{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T17:02:24Z","timestamp":1778173344339,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2015\/19\/B\/NZ2\/01824"],"award-info":[{"award-number":["2015\/19\/B\/NZ2\/01824"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Microcephaly presents in neurodevelopmental disorders with multiple aetiologies, including bi-allelic mutation in TUBGCP2, a component of the biologically fundamental and conserved microtubule-nucleation complex, \u03b3-TuRC. Elucidating underlying principles driving microcephaly requires clear phenotype recapitulation and assay reproducibility, areas where go-to experimental models fall short. We present an alternative simple vertebrate\/invertebrate dual system to investigate fundamental TUBGCP2-related processes driving human microcephaly and associated developmental traits. We show that antisense morpholino knockdown (KD) of the Danio rerio homolog, tubgcp2, recapitulates human TUBGCP2-associated microcephaly. Co-injection of wild type mRNA pre-empts microcephaly in 55% of KD zebrafish larvae, confirming causality. Body shortening observed in morphants is also rescued. Mitotic marker (pH3) staining further reveals aberrantly accumulated dividing brain cells in microcephalic tubgcp2 KD morphants, indicating that tubgcp2 depletion disrupts normal mitosis and\/or proliferation in zebrafish neural progenitor brain cells. Drosophila melanogaster double knockouts (KO) for TUBGCP2 homologs Grip84\/cg7716 also develop microcephalic brains with general microsomia. Exacerbated Grip84\/cg7716-linked developmental aberration versus single mutations strongly suggests interactive or coinciding gene functions. We infer that tubgcp2 and Grip84\/cg7716 affect brain size similarly to TUBGCP2 and recapitulate both microcephaly and microcephaly-associated developmental impact, validating the zebrafish\/fly research model for human microcephaly. Given the conserved cross-phyla homolog function, the data also strongly support mitotic and\/or proliferative disruption linked to aberrant microtubule nucleation in progenitor brain cells as key mechanistic defects for human microcephaly.<\/jats:p>","DOI":"10.3390\/cells11172727","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T21:27:17Z","timestamp":1662067637000},"page":"2727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Zebrafish\/Drosophila Dual System Model for Investigating Human Microcephaly"],"prefix":"10.3390","volume":"11","author":[{"given":"Slawomir","family":"Bartoszewski","sequence":"first","affiliation":[{"name":"Department of Biology, Institute of Biology and Biotechnology, University of Rzesz\u00f3w, 35-601 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-8722","authenticated-orcid":false,"given":"Mateusz","family":"Dawidziuk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0242-2587","authenticated-orcid":false,"given":"Natalia","family":"Kasica","sequence":"additional","affiliation":[{"name":"Department of Animal Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9100-766X","authenticated-orcid":false,"given":"Roma","family":"Durak","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Biology and Biotechnology, University of Rzesz\u00f3w, 35-601 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Jurek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Podwysocka","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothy Lys","family":"Guilbride","sequence":"additional","affiliation":[{"name":"Independent Researcher, Manhi\u00e7a MPT 1122, Mozambique"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-5449","authenticated-orcid":false,"given":"Piotr","family":"Podlasz","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Forensic Veterinary Medicine and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-5248","authenticated-orcid":false,"given":"Cecilia Lanny","family":"Winata","sequence":"additional","affiliation":[{"name":"Laboratory of Zebrafish Developmental Genomics, International Institute of Molecular and Cell Biology in Warsaw, 02-109 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-5834","authenticated-orcid":false,"given":"Pawel","family":"Gawlinski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1038\/s41436-019-0464-7","article-title":"Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly","volume":"21","author":"Boonsawat","year":"2019","journal-title":"Genet. 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