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Reduced mTORC1-signaling in progenitor cells leads to retinal lamination deficits
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).ORCID iD: 0000-0001-9401-6844
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).ORCID iD: 0000-0002-9934-7332
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
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2024 (English)In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Neuronal lamination is a hallmark of the mammalian central nervous system (CNS) and underlies connectivity and function. Initial formation of this tissue architecture involves the integration of various signaling pathways that regulate the differentiation and migration of neural progenitor cells.

Results: Here, we demonstrate that mTORC1 mediates critical roles during neuronal lamination using the mouse retina as a model system. Down-regulation of mTORC1-signaling in retinal progenitor cells by conditional deletion of Rptor led to decreases in proliferation and increased apoptosis during embryogenesis. These developmental deficits preceded aberrant lamination in adult animals which was best exemplified by the fusion of the outer and inner nuclear layer and the absence of an outer plexiform layer. Moreover, ganglion cell axons originating from each Rptor-ablated retina appeared to segregate to an equal degree at the optic chiasm with both contralateral and ipsilateral projections displaying overlapping termination topographies within several retinorecipient nuclei. In combination, these visual pathway defects led to visually mediated behavioral deficits.

Conclusions: This study establishes a critical role for mTORC1-signaling during retinal lamination and demonstrates that this pathway regulates diverse developmental mechanisms involved in driving the stratified arrangement of neurons during CNS development.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024.
Keywords [en]
Chx10, dLGN, lamination, mTORC1, retina, Rptor
National Category
Neurosciences Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-223249DOI: 10.1002/dvdy.707ISI: 001193263800001PubMedID: 38546215Scopus ID: 2-s2.0-85189534154OAI: oai:DiVA.org:umu-223249DiVA, id: diva2:1852594
Available from: 2024-04-18 Created: 2024-04-18 Last updated: 2024-04-18

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Nord, ChristofferJones, IwanHägglund, Anna-CarinCarlsson, Leif

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