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Reduced mTORC1-signalling in retinal progenitor cells leads to visual pathway dysfunction
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).ORCID iD: 0000-0003-0900-0552
2019 (English)In: Biology Open, ISSN 2046-6390, Vol. 8, no 8, article id bio044370Article in journal (Refereed) Published
Abstract [en]

Development of the vertebrate central nervous system involves the co-ordinated differentiation of progenitor cells and the establishment of functional neural networks. This neurogenic process is driven by both intracellular and extracellular cues that converge on the mammalian target of rapamycin complex 1 (mTORC1). Here we demonstrate that mTORC1-signalling mediates multi-faceted roles during central nervous system development using the mouse retina as a model system. Downregulation of mTORC1-signalling in retinal progenitor cells by conditional ablation of Rptor leads to proliferation deficits and an over-production of retinal ganglion cells during embryonic development. In contrast, reduced mTORC1-signalling in postnatal animals leads to temporal deviations in programmed cell death and the consequent production of asymmetric retinal ganglion cell mosaics and associated loss of axonal termination topographies in the dorsal lateral geniculate nucleus of adult mice. In combination these developmental defects induce visually mediated behavioural deficits. These collective observations demonstrate that mTORC1-signalling mediates critical roles during visual pathway development and function.

Place, publisher, year, edition, pages
The Company of Biologists , 2019. Vol. 8, no 8, article id bio044370
Keywords [en]
Raptor, mTORC1, Retina, RGCs, dLGN, Visual cliff test
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-164651DOI: 10.1242/bio.044370ISI: 000484809100019PubMedID: 31285269Scopus ID: 2-s2.0-85072065895OAI: oai:DiVA.org:umu-164651DiVA, id: diva2:1365748
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-10-25Bibliographically approved

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