Progenitor division and cell autonomous neurosecretion are required for rod photoreceptor sublaminar positioning.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
17 10 2023
Historique:
pmc-release: 09 04 2024
medline: 1 11 2023
pubmed: 9 10 2023
entrez: 9 10 2023
Statut: ppublish

Résumé

Migration is essential for the laminar stratification and connectivity of neurons in the central nervous system. In the retina, photoreceptors (PRs) migrate to positions according to birthdate, with early-born cells localizing to the basal-most side of the outer nuclear layer. It was proposed that apical progenitor mitoses physically drive these basal translocations non-cell autonomously, but direct evidence is lacking, and whether other mechanisms participate is unknown. Here, combining loss- or gain-of-function assays to manipulate cell cycle regulators (Sonic hedgehog, Cdkn1a/p21) with an in vivo lentiviral labelling strategy, we demonstrate that progenitor division is one of two forces driving basal translocation of rod soma. Indeed, replacing Shh activity rescues abnormal rod translocation in retinal explants. Unexpectedly, we show that rod differentiation also promotes rod soma translocation. While outer segment function or formation is dispensable,

Identifiants

pubmed: 37812728
doi: 10.1073/pnas.2308204120
pmc: PMC10589646
doi:

Substances chimiques

Hedgehog Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2308204120

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Auteurs

Akshay Gurdita (A)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Victor Q B Pham Truong (VQB)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Parnian Dolati (P)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Matey Juric (M)

Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Nobuhiko Tachibana (N)

Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Zhongda C Liu (ZC)

Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Arturo Ortín-Martínez (A)

Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Mostafa Ibrahimi (M)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Nenad T Pokrajac (NT)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Lacrimioara Comanita (L)

Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.

Marek Pacal (M)

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada.

Mengjia Huang (M)

Division of Experimental and Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Shuzo Sugita (S)

Division of Experimental and Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Rod Bremner (R)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada.
Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada.

Valerie A Wallace (VA)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada.

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Classifications MeSH