{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:46:17Z","timestamp":1785433577301,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,8]]},"group-title":"Neuroscience","reference-count":83,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01EY032057"],"award-info":[{"award-number":["R01EY032057"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32EY023211"],"award-info":[{"award-number":["T32EY023211"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30NS061800"],"award-info":[{"award-number":["P30NS061800"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Neurons are subject to extensive developmental regulation to ensure precise subtype-specific morphologies that are intimately tied to their function. Starburst amacrine cells (SACs) in the mammalian retina have a highly stereotyped, radially symmetric dendritic arbor that is essential for their role in direction-selective circuits in the retina. We show that PTEN, the primary negative regulator of the PI3K-AKT-mTOR pathway that is highly implicated in neurodevelopmental disorders, regulates SAC morphology in a cell-autonomous manner.<\/jats:p>\n                <jats:p>\n                  <jats:italic>Pten<\/jats:italic>\n                  -deficient SACs show a nearly twofold increase in the number of dendritic branches, while other morphological properties remain largely unchanged. These morphological changes arise late in SAC development after dendrite development is largely complete and persist into adulthood. Mechanistically, excessive dendritic branching appears to arise from dysregulated mTOR activity. Despite this dramatic increase in dendritic branches,\n                  <jats:italic>Pten<\/jats:italic>\n                  -deficient SACs maintain a normal population number, organization of synaptic outputs, and intact direction-selectivity in the retina. Collectively, these results show that PTEN is essential for the normal development of highly stereotyped neuronal morphology.\n                <\/jats:p>","DOI":"10.1101\/2025.05.08.652956","type":"posted-content","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T03:15:11Z","timestamp":1746760511000},"source":"Crossref","is-referenced-by-count":0,"title":["PTEN regulates starburst amacrine cell dendrite morphology during development"],"prefix":"10.64898","author":[{"given":"Teva W.","family":"Bracha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Luong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2751-0727","authenticated-orcid":false,"given":"Joseph","family":"Leffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-5768","authenticated-orcid":false,"given":"Benjamin","family":"Sivyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5094-5270","authenticated-orcid":false,"given":"Kevin M.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025052506350208000_2025.05.08.652956v1.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100913-013020"},{"key":"2025052506350208000_2025.05.08.652956v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.85"},{"key":"2025052506350208000_2025.05.08.652956v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2836"},{"key":"2025052506350208000_2025.05.08.652956v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2020.12.008"},{"key":"2025052506350208000_2025.05.08.652956v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2010.10.001"},{"key":"2025052506350208000_2025.05.08.652956v1.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189095"},{"key":"2025052506350208000_2025.05.08.652956v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00447-0"},{"key":"2025052506350208000_2025.05.08.652956v1.8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-072116-031437"},{"key":"2025052506350208000_2025.05.08.652956v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2019.04.002"},{"key":"2025052506350208000_2025.05.08.652956v1.10","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.12.2867"},{"key":"2025052506350208000_2025.05.08.652956v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.031"},{"key":"2025052506350208000_2025.05.08.652956v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.08.016"},{"key":"2025052506350208000_2025.05.08.652956v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00160-0"},{"key":"2025052506350208000_2025.05.08.652956v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.009"},{"key":"2025052506350208000_2025.05.08.652956v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nature11305"},{"key":"2025052506350208000_2025.05.08.652956v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.06.013"},{"key":"2025052506350208000_2025.05.08.652956v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2016.06.009"},{"key":"2025052506350208000_2025.05.08.652956v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2018.07.007"},{"key":"2025052506350208000_2025.05.08.652956v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/nature10877"},{"key":"2025052506350208000_2025.05.08.652956v1.20","doi-asserted-by":"crossref","unstructured":"Ray, T.A. , et al., Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact. Elife, 2018. 7.","DOI":"10.7554\/eLife.34241"},{"key":"2025052506350208000_2025.05.08.652956v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114615"},{"key":"2025052506350208000_2025.05.08.652956v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2023.07.011"},{"key":"2025052506350208000_2025.05.08.652956v1.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241974"},{"key":"2025052506350208000_2025.05.08.652956v1.24","doi-asserted-by":"crossref","unstructured":"James, R.E. , et al., Retinal ganglion cell-derived semaphorin 6A segregates starburst amacrine cell dendritic scaffolds to organize the mouse inner retina. Development, 2024. 151(22).","DOI":"10.1242\/dev.204293"},{"key":"2025052506350208000_2025.05.08.652956v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.085"},{"key":"2025052506350208000_2025.05.08.652956v1.26","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-082411-113907"},{"key":"2025052506350208000_2025.05.08.652956v1.27","doi-asserted-by":"crossref","unstructured":"Rademacher, S. and B.J. Eickholt , PTEN in Autism and Neurodevelopmental Disorders. Cold Spring Harb Perspect Med, 2019. 9(11).","DOI":"10.1101\/cshperspect.a036780"},{"key":"2025052506350208000_2025.05.08.652956v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01303-z"},{"key":"2025052506350208000_2025.05.08.652956v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.01.005"},{"key":"2025052506350208000_2025.05.08.652956v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.339"},{"key":"2025052506350208000_2025.05.08.652956v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.03.023"},{"key":"2025052506350208000_2025.05.08.652956v1.32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0061-11.2011"},{"key":"2025052506350208000_2025.05.08.652956v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.08.014"},{"key":"2025052506350208000_2025.05.08.652956v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2011.11.007"},{"key":"2025052506350208000_2025.05.08.652956v1.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032795"},{"key":"2025052506350208000_2025.05.08.652956v1.36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0936-16.2016"},{"key":"2025052506350208000_2025.05.08.652956v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114005"},{"key":"2025052506350208000_2025.05.08.652956v1.38","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu057"},{"key":"2025052506350208000_2025.05.08.652956v1.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5272-14.2015"},{"key":"2025052506350208000_2025.05.08.652956v1.40","unstructured":"Fernandez, A. , et al., Altered primary somatosensory neuron development in a Pten heterozygous model for autism spectrum disorder. bioRxiv, 2025."},{"key":"2025052506350208000_2025.05.08.652956v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.02.064"},{"key":"2025052506350208000_2025.05.08.652956v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/nature18609"},{"key":"2025052506350208000_2025.05.08.652956v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2024.08.002"},{"key":"2025052506350208000_2025.05.08.652956v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.07.019"},{"key":"2025052506350208000_2025.05.08.652956v1.45","doi-asserted-by":"crossref","unstructured":"Kosillo, P. , et al., Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2. Elife, 2022. 11.","DOI":"10.7554\/eLife.75398"},{"key":"2025052506350208000_2025.05.08.652956v1.46","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-10-121"},{"key":"2025052506350208000_2025.05.08.652956v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/nature09818"},{"key":"2025052506350208000_2025.05.08.652956v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.015"},{"key":"2025052506350208000_2025.05.08.652956v1.49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000221"},{"key":"2025052506350208000_2025.05.08.652956v1.50","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523811000216"},{"key":"2025052506350208000_2025.05.08.652956v1.51","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0933-15.2015"},{"key":"2025052506350208000_2025.05.08.652956v1.52","doi-asserted-by":"crossref","unstructured":"Kostadinov, D. and J.R. Sanes , Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function. Elife, 2015. 4.","DOI":"10.7554\/eLife.08964"},{"key":"2025052506350208000_2025.05.08.652956v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.08.021"},{"key":"2025052506350208000_2025.05.08.652956v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2017.05.026"},{"key":"2025052506350208000_2025.05.08.652956v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00295-1"},{"key":"2025052506350208000_2025.05.08.652956v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.03.039"},{"key":"2025052506350208000_2025.05.08.652956v1.57","doi-asserted-by":"publisher","DOI":"10.4161\/cib.28358"},{"key":"2025052506350208000_2025.05.08.652956v1.58","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2270-05.2005"},{"key":"2025052506350208000_2025.05.08.652956v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.09.019"},{"key":"2025052506350208000_2025.05.08.652956v1.60","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1835-21.2022"},{"key":"2025052506350208000_2025.05.08.652956v1.61","doi-asserted-by":"crossref","unstructured":"Urwyler, O. , et al., Branch-restricted localization of phosphatase Prl-1 specifies axonal synaptogenesis domains. Science, 2019. 364(6439).","DOI":"10.1126\/science.aau9952"},{"key":"2025052506350208000_2025.05.08.652956v1.62","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44909"},{"key":"2025052506350208000_2025.05.08.652956v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111574"},{"key":"2025052506350208000_2025.05.08.652956v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.05.011"},{"key":"2025052506350208000_2025.05.08.652956v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/s44318-024-00050-3"},{"key":"2025052506350208000_2025.05.08.652956v1.66","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1305-21.2022"},{"key":"2025052506350208000_2025.05.08.652956v1.67","doi-asserted-by":"publisher","DOI":"10.1126\/science.1161566"},{"key":"2025052506350208000_2025.05.08.652956v1.68","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6271-09.2010"},{"key":"2025052506350208000_2025.05.08.652956v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2603"},{"key":"2025052506350208000_2025.05.08.652956v1.70","doi-asserted-by":"publisher","DOI":"10.1038\/nature10594"},{"key":"2025052506350208000_2025.05.08.652956v1.71","doi-asserted-by":"crossref","unstructured":"Santos, J.R. , et al., Predicting the Regenerative Potential of Retinal Ganglion Cells Based on Developmental Growth Trajectories. bioRxiv, 2025.","DOI":"10.1101\/2025.02.28.640775"},{"key":"2025052506350208000_2025.05.08.652956v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00316-6"},{"key":"2025052506350208000_2025.05.08.652956v1.73","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523802194119"},{"key":"2025052506350208000_2025.05.08.652956v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.07.037"},{"key":"2025052506350208000_2025.05.08.652956v1.75","doi-asserted-by":"publisher","DOI":"10.1038\/nature00931"},{"key":"2025052506350208000_2025.05.08.652956v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.08.007"},{"key":"2025052506350208000_2025.05.08.652956v1.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.03.001"},{"key":"2025052506350208000_2025.05.08.652956v1.78","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3144-14.2015"},{"key":"2025052506350208000_2025.05.08.652956v1.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.01.010"},{"key":"2025052506350208000_2025.05.08.652956v1.80","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<130::AID-GENE9>3.0.CO;2-I"},{"key":"2025052506350208000_2025.05.08.652956v1.81","doi-asserted-by":"publisher","DOI":"10.1038\/ng782"},{"key":"2025052506350208000_2025.05.08.652956v1.82","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"key":"2025052506350208000_2025.05.08.652956v1.83","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-0876-1"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.05.08.652956","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:11:14Z","timestamp":1782277874000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.05.08.652956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,8]]},"references-count":83,"URL":"https:\/\/doi.org\/10.1101\/2025.05.08.652956","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1242\/dev.204980","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,5,8]]},"subtype":"preprint"}}