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Recently, we proposed the homozygous cdkl5sa21938 mutant zebrafish as a model of CDKL5 deficiency disorder (CDD), a developmental epileptic encephalopathy with diverse symptoms. This study aimed to explore Cdkl5-associated molecular mechanisms in zebrafish and assess their similarity to those in mammals. We conducted RNA sequencing on whole cdkl5\u2212\/\u2212 zebrafish and wild-type siblings at 5 and 35 days post-fertilization (dpf) to compare their gene expression profiles. Most significant differentially expressed genes (DEGs) were related to muscle, neuronal, and visual systems which are affected in CDD. Gene Ontology analysis revealed downregulated DEGs enriched in muscle development, extracellular matrix, and actin cytoskeleton functions at both stages, while upregulated DEGs were enriched in eye development functions at 35 dpf. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed enrichment of downregulated DEGs in focal adhesion and extracellular matrix (ECM)-receptor interaction pathways at both stages. Neuronal development DEGs were mainly downregulated at both stages, while synaptic signaling DEGs were upregulated at 35 dpf. Crossing cdkl5\u2212\/\u2212 mutants with the Hb9:GFP transgenic line showed fewer motor neuron cells with shorter axons compared to the wild type, which may explain the impaired motor phenotype observed in zebrafish and CDD patients. Moreover, we identified key downregulated DEGs related to cartilage development at both stages and bone development at 35 dpf, potentially explaining the skeletal defects seen in zebrafish and CDD individuals. In conclusion, Cdkl5 loss in zebrafish leads to dysregulation of genes involved in CDKL5-associated functions in mammals, providing new insights into its less studied functions and phenotypes.<\/jats:p>","DOI":"10.3390\/ijms26136069","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T10:44:41Z","timestamp":1750761881000},"page":"6069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic Profiling of Zebrafish Mutant for cdkl5 Reveals Dysregulated Gene Expression Associated with Neuronal, Muscle, Visual and Skeletal Development"],"prefix":"10.3390","volume":"26","author":[{"given":"Tatiana","family":"Varela","sequence":"first","affiliation":[{"name":"Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences, University of Algarve, 8005-139 Faro, Portugal"}]},{"given":"D\u00e9bora","family":"Varela","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences, University of Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5057-0912","authenticated-orcid":false,"given":"Nat\u00e9rcia","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center, University of Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3114-6662","authenticated-orcid":false,"given":"M. Leonor","family":"Cancela","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center, University of Algarve, 8005-139 Faro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hector, R.D., Dando, O., Landsberger, N., Kilstrup-Nielsen, C., Kind, P.C., Bailey, M.E.S., and Cobb, S.R.C. (2016). Characterisation of CDKL5 transcript isoforms in human and mouse. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157758"},{"key":"ref_2","first-page":"728267","article-title":"What we know and would like to know about CDKL5 and its involvement in epileptic encephalopathy","volume":"2012","author":"Rusconi","year":"2012","journal-title":"Neural Plast."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"30101","DOI":"10.1074\/jbc.M804613200","article-title":"CDKL5 expression is modulated during neuronal development and its subcellular distribution is tightly regulated by the C-terminal tail","volume":"283","author":"Rusconi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12777","DOI":"10.1523\/JNEUROSCI.1102-10.2010","article-title":"CDKL5, a Protein Associated with Rett Syndrome, Regulates Neuronal Morphogenesis via Rac1 Signaling","volume":"30","author":"Chen","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/ncb2566","article-title":"CDKL5 ensures excitatory synapse stability by reinforcing NGL-1-PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons","volume":"14","author":"Ricciardi","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36550","DOI":"10.1074\/jbc.M111.235630","article-title":"Extrasynaptic N-Methyl-D-aspartate (NMDA) receptor stimulation induces cytoplasmic translocation of the CDKL5 kinase and its proteasomal degradation","volume":"286","author":"Rusconi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1042\/BST20220791","article-title":"CDKL5 deficiency disorder: Molecular insights and mechanisms of pathogenicity to fast-track therapeutic development","volume":"50","author":"Massey","year":"2022","journal-title":"Biochem. Soc. Trans."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nawaz, M.S., Giarda, E., Bedogni, F., Montanara, P.L., Ricciardi, S., Ciceri, D., Alberio, T., Landsberger, N., Rusconi, L., and Kilstrup-Nielsen, C. (2016). CDKL5 and shootin1 interact and concur in regulating neuronal polarization. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148634"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.abb.2013.04.012","article-title":"Identification of amphiphysin 1 as an endogenous substrate for CDKL5, a protein kinase associated with X-linked neurodevelopmental disorder","volume":"535","author":"Sekiguchi","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1021\/bi501308k","article-title":"Critical determinants of substrate recognition by cyclin-dependent kinase-like 5 (CDKL5)","volume":"54","author":"Katayama","year":"2015","journal-title":"Biochemistry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e99559","DOI":"10.15252\/embj.201899559","article-title":"Phosphoproteomic screening identifies physiological substrates of the CDKL 5 kinase","volume":"37","author":"Morgan","year":"2018","journal-title":"EMBO J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e99763","DOI":"10.15252\/embj.201899763","article-title":"Chemical genetic identification of CDKL 5 substrates reveals its role in neuronal microtubule dynamics","volume":"37","author":"Baltussen","year":"2018","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.bbrc.2008.10.113","article-title":"Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1","volume":"377","author":"Kameshita","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1093\/hmg\/ddi198","article-title":"CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome","volume":"14","author":"Mari","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1093\/brain\/awn197","article-title":"Key clinical features to identify girls with CDKL5 mutations","volume":"131","author":"Nectoux","year":"2008","journal-title":"Brain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ejhg.2012.156","article-title":"The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy","volume":"21","author":"Fehr","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jakimiec, M., Paprocka, J., and \u015amigiel, R. (2020). CDKL5 deficiency disorder\u2014A complex epileptic encephalopathy. Brain Sci., 10.","DOI":"10.3390\/brainsci10020107"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S1474-4422(22)00035-7","article-title":"CDKL5 deficiency disorder: Clinical features, diagnosis, and management","volume":"21","author":"Leonard","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s11689-021-09384-z","article-title":"Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder","volume":"13","author":"Olson","year":"2021","journal-title":"J. Neurodev. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Amendola, E., Zhan, Y., Mattucci, C., Castroflorio, E., Calcagno, E., Fuchs, C., Lonetti, G., Silingardi, D., Vyssotski, A.L., and Farley, D. (2014). Mapping pathological phenotypes in a mouse model of CDKL5 disorder. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091613"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9726950","DOI":"10.1155\/2018\/9726950","article-title":"Heterozygous CDKL5 knockout female mice are a valuable animal model for CDKL5 disorder","volume":"2018","author":"Fuchs","year":"2018","journal-title":"Neural Plast."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Okuda, K., Takao, K., Watanabe, A., Miyakawa, T., Mizuguchi, M., and Tanaka, T. (2018). Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196587"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21516","DOI":"10.1073\/pnas.1216988110","article-title":"Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice","volume":"109","author":"Wang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1093\/hmg\/ddx279","article-title":"Mice lacking cyclin-dependent kinase-like 5 manifest autistic and ADHD-like behaviors","volume":"26","author":"Jhang","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1093\/hmg\/ddad149","article-title":"CDKL5-mediated developmental tuning of neuronal excitability and concomitant regulation of transcriptome","volume":"32","author":"Liao","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s11033-018-4180-1","article-title":"Expression pattern of cdkl5 during zebrafish early development: Implications for use as model for atypical Rett syndrome","volume":"45","author":"Vitorino","year":"2018","journal-title":"Mol. Biol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Varela, T., Varela, D., Martins, G., Concei\u00e7\u00e3o, N., and Cancela, M.L. (2022). Cdkl5 mutant zebrafish shows skeletal and neuronal alterations mimicking human CDKL5 deficiency disorder. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-13364-1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1074\/jbc.272.6.3599","article-title":"Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography","volume":"272","author":"Petersen","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"26273","DOI":"10.1074\/jbc.273.41.26273","article-title":"The 100-kDa neurotensin receptor is gp95\/sortilin, a non-G-protein-coupled receptor","volume":"273","author":"Mazella","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0378-1119(98)00510-1","article-title":"Isolation and characterization of the human X-arrestin gene","volume":"224","author":"Sakuma","year":"1998","journal-title":"Gene"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Morales-C\u00e1mara, S., Alexandre-Moreno, S., Bonet-Fern\u00e1ndez, J.M., Atienzar-Aroca, R., Aroca-Aguilar, J.D., Ferre-Fern\u00e1ndez, J.J., M\u00e9ndez, C.D., Morales, L., Fern\u00e1ndez-S\u00e1nchez, L., and Cuenca, N. (2020). Role of GUCA1C in primary congenital glaucoma and in the retina: Functional evaluation in zebrafish. Genes, 11.","DOI":"10.20944\/preprints202003.0424.v1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1016\/j.radcr.2023.09.026","article-title":"Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature","volume":"18","author":"Libell","year":"2023","journal-title":"Radiol. Case Rep."},{"key":"ref_33","first-page":"141","article-title":"Cysteine cathepsins in extracellular matrix remodeling: Extracellular matrix degradation and beyond","volume":"75\u201376","author":"Turk","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.matbio.2004.09.004","article-title":"Collagen, type V, \u03b11 (COL5A1) is regulated by TGF-\u03b2 in osteoblasts","volume":"23","author":"Kahai","year":"2004","journal-title":"Matrix Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e013318","DOI":"10.1161\/JAHA.119.013318","article-title":"Expression of normally repressed myosin heavy chain 7b in the mammalian heart induces dilated cardiomyopathy","volume":"8","author":"Peter","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.ydbio.2009.11.015","article-title":"Foxj3 transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity","volume":"337","author":"Alexander","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11205","DOI":"10.1074\/jbc.M611279200","article-title":"The DYNLT3 light chain directly links cytoplasmic dynein to a spindle checkpoint protein, Bub3","volume":"282","author":"Lo","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e163592","DOI":"10.1172\/JCI163592","article-title":"Superenhancer activation of KLHDC8A drives glioma ciliation and hedgehog signaling","volume":"133","author":"Lee","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6777","DOI":"10.1073\/pnas.1131928100","article-title":"Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function","volume":"100","author":"Zhao","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ydbio.2006.06.007","article-title":"The role of megalin (LRP-2\/Gp330) during development","volume":"296","author":"Fisher","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_41","first-page":"2313","article-title":"The zebrafish lens proteome during development and aging","volume":"15","author":"Greiling","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6767","DOI":"10.1074\/jbc.RA120.012695","article-title":"Effects of deficiency in the RLBP1-encoded visual cycle protein CRALBP on visual dysfunction in humans and mice","volume":"295","author":"Kim","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Irum, B., Khan, S.Y., Ali, M., Kaul, H., Kabir, F., Rauf, B., Fatima, F., Nadeem, R., Khan, A.O., and Al Obaisi, S. (2016). Mutation in LIM2 is responsible for autosomal recessive congenital cataracts. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162620"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"578411","DOI":"10.1016\/j.jneuroim.2024.578411","article-title":"Co-localization and co-expression of Olfml3 with Iba1 in brain of mice","volume":"394","author":"Yadav","year":"2024","journal-title":"J. Neuroimmunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1038\/s12276-022-00902-0","article-title":"Drawing a line between histone demethylase KDM5A and KDM5B: Their roles in development and tumorigenesis","volume":"54","author":"Yoo","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/genetics\/163.2.663","article-title":"Gene duplication and spectral diversification of cone visual pigments of zebrafish","volume":"163","author":"Chinen","year":"2002","journal-title":"Genetics"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lamber, E.P., Guicheney, P., and Pinotsis, N. (2022). The role of the M-band myomesin proteins in muscle integrity and cardiac disease. J. Biomed. Sci., 29.","DOI":"10.1186\/s12929-022-00801-6"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110477","DOI":"10.1016\/j.ygeno.2022.110477","article-title":"Zebrafish Danio rerio myotomal muscle structure and growth from a spatial transcriptomics perspective","volume":"114","author":"Liu","year":"2022","journal-title":"Genomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/gene.20055","article-title":"Transcription cofactor Vgl-2 is required for skeletal muscle differentiation","volume":"39","author":"Chen","year":"2004","journal-title":"Genesis"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Niu, X., Zhang, F., Ping, L., Wang, Y., Zhang, B., Wang, J., and Chen, X. (2023). vwa1 Knockout in Zebrafish causes abnormal craniofacial chondrogenesis by regulating FGF pathway. Genes, 14.","DOI":"10.3390\/genes14040838"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.biocel.2012.01.012","article-title":"Neurofascin: A switch between neuronal plasticity and stability","volume":"44","author":"Kriebel","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1093\/brain\/awz248","article-title":"Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination","volume":"142","author":"Efthymiou","year":"2019","journal-title":"Brain"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4759","DOI":"10.1073\/pnas.96.9.4759","article-title":"Ion channel genes and human neurological disease: Recent progress, prospects, and challenges","volume":"96","author":"Cooper","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.mpaic.2013.05.020","article-title":"Ion channels, receptors, agonists and antagonists","volume":"14","author":"Weir","year":"2013","journal-title":"Anaesth. Intensive Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"dmm049094","DOI":"10.1242\/dmm.049094","article-title":"Novel preclinical model for CDKL5 deficiency disorder","volume":"15","author":"Serrano","year":"2022","journal-title":"Dis. Models Mech."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1002\/dvdy.22113","article-title":"Normal table of postembryonic zebrafish development: Staging by externally visible anatomy of the living fish","volume":"238","author":"Parichy","year":"2009","journal-title":"Dev. Dyn."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Quintiliani, M., Ricci, D., Petrianni, M., Leone, S., Orazi, L., Amore, F., Gambardella, M.L., Contaldo, I., Veredice, C., and Perulli, M. (2022). Cortical visual impairment in CDKL5 deficiency disorder. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.805745"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Loi, M., Bastianini, S., Candini, G., Rizzardi, N., Medici, G., Papa, V., Gennaccaro, L., Mottolese, N., Tassinari, M., and Uguagliati, B. (2023). Cardiac functional and structural abnormalities in a mouse model of CDKL5 deficiency disorder. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065552"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/ajmg.a.62995","article-title":"Analysis of electrocardiograms in individuals with CDKL5 deficiency disorder","volume":"191","author":"Stansauk","year":"2023","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1146\/annurev-neuro-060909-153204","article-title":"Mechanisms of synapse and dendrite maintenance and their disruption in psychiatric and neurodegenerative disorders","volume":"33","author":"Lin","year":"2010","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.gde.2011.01.002","article-title":"Synapse development in health and disease","volume":"21","author":"Melom","year":"2011","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Xiong, G.J., and Sheng, Z.H. (2024). Presynaptic perspective: Axonal transport defects in neurodevelopmental disorders. J. Cell Biol., 223.","DOI":"10.1083\/jcb.202401145"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Engle, E.C. (2010). Human genetic disorders of axon guidance. Cold Spring Harb. Perspect. Biol., 2.","DOI":"10.1101\/cshperspect.a001784"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0092-8674(87)90107-3","article-title":"Neurofascin: A novel chick cell-surface glycoprotein involved in neurite-neurite interactions","volume":"51","author":"Rathjen","year":"1987","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.mcn.2005.06.007","article-title":"Cell adhesion and neurite outgrowth are promoted by neurofascin NF155 and inhibited by NF186","volume":"30","author":"Koticha","year":"2005","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.ajhg.2013.03.021","article-title":"ZC4H2 mutations are associated with arthrogryposis multiplex congenita and intellectual disability through impairment of central and peripheral synaptic plasticity","volume":"92","author":"Hirata","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.cell.2009.06.047","article-title":"The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis","volume":"138","author":"Guerrier","year":"2009","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.1016\/j.febslet.2007.08.075","article-title":"Mouse Prickle1 and Prickle2 are expressed in postmitotic neurons and promote neurite outgrowth","volume":"581","author":"Okuda","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kvarnung, M., Shahsavani, M., Taylan, F., Moslem, M., Breeuwsma, N., Laan, L., Schuster, J., Jin, Z., Nilsson, D., and Lieden, A. (2019). Ataxia in patients with bi-allelic NFASC mutations and absence of full-length NF186. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00896"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1093\/hmg\/ddy277","article-title":"Homozygous mutation in the Neurofascin gene affecting the glial isoform of Neurofascin causes severe neurodevelopment disorder with hypotonia, amimia and areflexia","volume":"27","author":"Smigiel","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"120","DOI":"10.26815\/acn.2022.00129","article-title":"Variable phenotypes of ZC4H2-associated rare disease in six patients","volume":"30","author":"Ahn","year":"2022","journal-title":"Ann. Child Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.ajhg.2008.10.003","article-title":"A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome","volume":"83","author":"Bassuk","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/s41431-021-00912-y","article-title":"PRICKLE2 revisited\u2014Further evidence implicating PRICKLE2 in neurodevelopmental disorders","volume":"29","author":"Bayat","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/ENEURO.0193-20.2021","article-title":"Fez1 forms complexes with crmp1 and dcc to regulate axon and dendrite development","volume":"8","author":"Chua","year":"2021","journal-title":"eNeuro"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/hmg\/ddaa281","article-title":"Loss of FEZ1, a gene deleted in Jacobsen syndrome, causes locomotion defects and early mortality by impairing motor neuron development","volume":"30","author":"Gunaseelan","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/cne.903020315","article-title":"Identification of spinal neurons in the embryonic and larval zebrafish","volume":"302","author":"Bernhardt","year":"1990","journal-title":"J. Comp. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1523\/JNEUROSCI.06-08-02278.1986","article-title":"Development and axonal outgrowth of identified motoneurons in the zebrafish","volume":"6","author":"Myers","year":"1986","journal-title":"J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1111\/bpa.12716","article-title":"CDKL5 deficiency predisposes neurons to cell death through the deregulation of SMAD3 signaling","volume":"29","author":"Fuchs","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1002\/glia.24336","article-title":"Emerging concepts in oligodendrocyte and myelin formation, inputs from the zebrafish model","volume":"71","author":"Masson","year":"2023","journal-title":"Glia"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41586-020-2494-3","article-title":"Suppression of proteolipid protein rescues Pelizaeus\u2013Merzbacher disease","volume":"585","author":"Elitt","year":"2020","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Galvez-Contreras, A.Y., Zarate-Lopez, D., Torres-Chavez, A.L., and Gonzalez-Perez, O. (2020). Role of oligodendrocytes and myelin in the pathophysiology of autism spectrum disorder. Brain Sci., 10.","DOI":"10.3390\/brainsci10120951"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00018-024-05222-2","article-title":"Functional myelin in cognition and neurodevelopmental disorders","volume":"81","author":"Khelfaoui","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_84","unstructured":"Pickel, V., and Segal, M. (2014). Chapter Two\u2014The molecular mechanisms underlying synaptic transmission: A view of the presynaptic terminal. The Synapse, Academic Press."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev.neuro.26.041002.131412","article-title":"The synaptic vesicle cycle","volume":"27","year":"2004","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1146\/annurev.neuro.26.041002.131445","article-title":"Cell biology of the presynaptic terminal","volume":"26","author":"Murthy","year":"2003","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/epi.12034","article-title":"Regulators of synaptic transmission: Roles in the pathogenesis and treatment of epilepsy","volume":"53","author":"Powell","year":"2012","journal-title":"Epilepsia"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Pizzo, R., Gurgone, A., Castroflorio, E., Amendola, E., Gross, C., Sasso\u00e8-Pognetto, M., and Giustetto, M. (2016). Lack of Cdkl5 disrupts the organization of excitatory and inhibitory synapses and parvalbumin interneurons in the primary visual cortex. Front. Cell Neurosci., 10.","DOI":"10.3389\/fncel.2016.00261"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/epi.16805","article-title":"CDKL5 deficiency in forebrain glutamatergic neurons results in recurrent spontaneous seizures","volume":"62","author":"Wang","year":"2021","journal-title":"Epilepsia"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9031","DOI":"10.1523\/JNEUROSCI.1010-21.2021","article-title":"CDKL5 deficiency augments inhibitory input into the dentate gyrus that can be reversed by deep brain stimulation","volume":"41","author":"Hao","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.nbd.2017.07.002","article-title":"CDKL5 controls postsynaptic localization of GluN2B-containing NMDA receptors in the hippocampus and regulates seizure susceptibility","volume":"106","author":"Okuda","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1038\/s41467-019-10689-w","article-title":"Altered NMDAR signaling underlies autistic-like features in mouse models of CDKL5 deficiency disorder","volume":"10","author":"Tang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7420","DOI":"10.1523\/JNEUROSCI.0539-17.2017","article-title":"Loss of CDKL5 in glutamatergic neurons disrupts hippocampal microcircuitry and leads to memory impairment in mice","volume":"37","author":"Tang","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/nan.12054","article-title":"Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis","volume":"40","author":"Kaminski","year":"2014","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"100922","DOI":"10.1016\/j.gim.2023.100922","article-title":"Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder","volume":"25","author":"Pavinato","year":"2023","journal-title":"Genet. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1172\/JCI90259","article-title":"Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder","volume":"127","author":"Lipstein","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1523\/JNEUROSCI.1537-22.2023","article-title":"Epilepsy-related CDKL5 deficiency slows synaptic vesicle endocytosis in central nerve terminals","volume":"43","author":"Kontaxi","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuroscience.2020.05.032","article-title":"Ion channels involvement in neurodevelopmental disorders","volume":"440","author":"Liantonio","year":"2020","journal-title":"NeuroScience"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1093\/hmg\/11.20.2435","article-title":"Ion channel diseases","volume":"11","author":"Jentsch","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1038\/s41436-021-01232-8","article-title":"Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations","volume":"23","author":"Rodan","year":"2021","journal-title":"Genet. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1111\/epi.16316","article-title":"Both gain-of-function and loss-of-function de novo CACNA1A mutations cause severe developmental epileptic encephalopathies in the spectrum of Lennox-Gastaut syndrome","volume":"60","author":"Jiang","year":"2019","journal-title":"Epilepsia"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.biopsych.2014.11.020","article-title":"CACNA1D de novo mutations in autism spectrum disorders activate cav1.3 l-type calcium channels","volume":"77","author":"Pinggera","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7830","DOI":"10.1038\/s41467-023-43475-w","article-title":"Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability","volume":"14","author":"Baltussen","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"fcad283","DOI":"10.1093\/braincomms\/fcad283","article-title":"Epilepsy and sudden unexpected death in epilepsy in a mouse model of human SCN1B-linked developmental and epileptic encephalopathy","volume":"5","author":"Chen","year":"2023","journal-title":"Brain Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1111\/epi.16319","article-title":"Phenotypic and genetic spectrum of SCN8A-related disorders, treatment options, and outcomes","volume":"60","author":"Gardella","year":"2019","journal-title":"Epilepsia"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/acn3.276","article-title":"Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy","volume":"3","author":"Wagnon","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Zhu, Z., Bolt, E., Newmaster, K., Osei-Bonsu, W., Cohen, S., Cuddapah, V.A., Gupta, S., Paudel, S., Samanta, D., and Dang, L.T. (2022). SCN1B genetic variants: A review of the spectrum of clinical phenotypes and a report of early myoclonic encephalopathy. Children, 9.","DOI":"10.3390\/children9101507"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6213","DOI":"10.1523\/JNEUROSCI.0405-16.2016","article-title":"\u03b21-C121W is down but not out: Epilepsy-associated scn1b-C121W results in a deleterious gain-of-function","volume":"36","author":"Kruger","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"107946","DOI":"10.1016\/j.yebeh.2021.107946","article-title":"Sodium channel blockers for the treatment of epilepsy in CDKL5 deficiency disorder: Findings from a multicenter cohort","volume":"118","author":"Toledano","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.ajhg.2024.04.019","article-title":"Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity","volume":"111","author":"Kalm","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.1523\/JNEUROSCI.4423-14.2015","article-title":"Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits","volume":"35","author":"Miceli","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1111\/epi.17656","article-title":"A novel KCNC1 gain-of-function variant causing developmental and epileptic encephalopathy: \u201cPrecision medicine\u201d approach with fluoxetine","volume":"64","author":"Ambrosino","year":"2023","journal-title":"Epilepsia"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1111\/epi.17118","article-title":"Distinct epilepsy phenotypes and response to drugs in KCNA1 gain- and loss-of function variants","volume":"63","author":"Miceli","year":"2022","journal-title":"Epilepsia"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Veale, E.L., Golluscio, A., Grand, K., Graham, J.M., and Mathie, A. (2022). A KCNB1 gain of function variant causes developmental delay and speech apraxia but not seizures. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1093313"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/epi4.12934","article-title":"Potassium channel-related epilepsy: Pathogenesis and clinical features","volume":"9","author":"Zhao","year":"2024","journal-title":"Epilepsia Open"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Wu, W., Yao, H., Negraes, P.D., Wang, J., Trujillo, C.A., de Souza, J.S., Muotri, A.R., and Haddad, G.G. (2022). Neuronal hyperexcitability and ion channel dysfunction in CDKL5-deficiency patient iPSC-derived cortical organoids. Neurobiol. Dis., 174.","DOI":"10.1016\/j.nbd.2022.105882"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.neuron.2015.07.033","article-title":"Excitatory\/inhibitory balance and circuit homeostasis in autism spectrum disorders","volume":"87","author":"Nelson","year":"2015","journal-title":"Neuron"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e2413011121","DOI":"10.1073\/pnas.2413011121","article-title":"Understanding paralogous epilepsy-associated GABAA receptor variants: Clinical implications, mechanisms, and potential pitfalls","volume":"121","author":"Kan","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Sun, J.H., Chen, J., Valenzuela, F.E.A., Brown, C., Masser-Frye, D., Jones, M., Romero, L.P., Rinaldi, B., Li, W.L., and Li, Q.Q. (2021). X-linked neonatal-onset epileptic encephalopathy associated with a gain-of-function variant p.R660T in GRIA3. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009608"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1111\/epi.17776","article-title":"GRIN1 variants associated with neurodevelopmental disorders reveal channel gating pathomechanisms","volume":"64","author":"Ragnarsson","year":"2023","journal-title":"Epilepsia"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1093\/brain\/awad403","article-title":"Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes","volume":"147","author":"Rinaldi","year":"2024","journal-title":"Brain"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00439-021-02416-7","article-title":"Amelioration of a neurodevelopmental disorder by carbamazepine in a case having a gain-of-function GRIA3 variant","volume":"141","author":"Hamanaka","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/brain\/awab391","article-title":"Gain-of-function variants in GABRD reveal a novel pathway for neurodevelopmental disorders and epilepsy","volume":"145","author":"Ahring","year":"2022","journal-title":"Brain"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/ana.26774","article-title":"GABRA1-related disorders: From genetic to functional pathways","volume":"95","author":"Musto","year":"2024","journal-title":"Ann. Neurol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4814","DOI":"10.1523\/JNEUROSCI.2041-18.2019","article-title":"AMPA receptor dysregulation and therapeutic interventions in a mouse model of CDKL5 deficiency disorder","volume":"39","author":"Yennawar","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Gennaccaro, L., Fuchs, C., Loi, M., Roncac\u00e8, V., Trazzi, S., Ait-Bali, Y., Galvani, G., Berardi, A.C., Medici, G., and Tassinari, M. (2021). A GABAB receptor antagonist rescues functional and structural impairments in the perirhinal cortex of a mouse model of CDKL5 deficiency disorder. Neurobiol. Dis., 153.","DOI":"10.1016\/j.nbd.2021.105304"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/bdrc.20048","article-title":"Transcriptional control of chondrocyte fate and differentiation","volume":"75","author":"Lefebvre","year":"2005","journal-title":"Birth Defects Res. C"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0070-2153(10)90008-2","article-title":"Vertebrate skeletogenesis","volume":"90","author":"Lefebvre","year":"2010","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Garc\u00eda, F., Fern\u00e1ndez-Iglesias, \u00c1., Rodr\u00edguez Su\u00e1rez, J., Gil Pe\u00f1a, H., L\u00f3pez, J.M., and P\u00e9rez, R.F. (2024). The crosstalk between cartilage and bone in skeletal growth. Biomedicines, 12.","DOI":"10.3390\/biomedicines12122662"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Tonelli, F., Bek, J.W., Besio, R., De Clercq, A., Leoni, L., Salmon, P., Coucke, P.J., Willaert, A., and Forlino, A. (2020). Zebrafish: A resourceful vertebrate model to investigate skeletal disorders. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00489"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/jbmr.4256","article-title":"Skeletal biology and disease modeling in zebrafish","volume":"36","author":"Dietrich","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Silvent, J., Akiva, A., Brumfeld, V., Reznikov, N., Rechav, K., Yaniv, K., Addadi, L., and Weiner, S. (2017). Zebrafish skeleton development: High resolution micro-CT and FIB-SEM block surface serial imaging for phenotype identification. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177731"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1128\/MCB.17.4.2336","article-title":"SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro1(II) collagen gene","volume":"17","author":"Huang","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"12712","DOI":"10.1074\/jbc.275.17.12712","article-title":"Identification of an enhancer sequence within the first Intron required for cartilage-specific transcription of the 2(XI) collagen gene","volume":"275","author":"Liu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1093\/nar\/gkm014","article-title":"A Col9a1 enhancer element activated by two interdependent SOX9 dimers","volume":"35","author":"Genzer","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1002\/ar.24086","article-title":"Genetic disorders of the extracellular matrix","volume":"303","author":"Bateman","year":"2020","journal-title":"Anat. Rec."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"247","DOI":"10.6065\/apem.2244120.060","article-title":"Growth plate extracellular matrix defects and short stature in children","volume":"27","author":"Saltarelli","year":"2022","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"101698","DOI":"10.1016\/j.bonr.2023.101698","article-title":"Hypertrophic chondrocytes at the junction of musculoskeletal structures","volume":"19","author":"Chen","year":"2023","journal-title":"Bone Rep."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.tcb.2003.12.003","article-title":"Matrix remodeling during endochondral ossification","volume":"14","author":"Ortega","year":"2004","journal-title":"Trends Cell Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biocel.2007.06.009","article-title":"Endochondral ossification: How cartilage is converted into bone in the developing skeleton","volume":"40","author":"Mackie","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00441-009-0832-8","article-title":"Regulation of bone development and extracellular matrix protein genes by RUNX2","volume":"339","author":"Komori","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"Wnt signaling in bone homeostasis and disease: From human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat. Med."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Maeda, K., Kobayashi, Y., Koide, M., Uehara, S., Okamoto, M., Ishihara, A., Kayama, T., Saito, M., and Marumo, K. (2019). The regulation of bone metabolism and disorders by Wnt signaling. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225525"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Huybrechts, Y., Mortier, G., Boudin, E., and Van Hul, W. (2020). Wnt signaling and bone: Lessons from skeletal dysplasias and disorders. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00165"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2741\/4214","article-title":"Wnt and the Wnt signaling pathway in bone development and disease","volume":"19","author":"Wang","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.bbi.2024.06.022","article-title":"Neutrophil immune profile guides spinal cord regeneration in zebrafish","volume":"120","author":"Laborde","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4471","DOI":"10.1242\/dev.02044","article-title":"Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations","volume":"132","author":"Fox","year":"2005","journal-title":"Development"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjaminit","year":"1995","journal-title":"J. R. Statist Soc. B"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41592-021-01105-7","article-title":"SNT: A unifying toolbox for quantification of neuronal anatomy","volume":"18","author":"Arshadi","year":"2021","journal-title":"Nat. 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