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

作者：Akshay Gurdita, Victor Q. B. Pham Truong, Parnian Dolati, Matey Juric, Nobuhiko Tachibana, Zhongda C. Liu, Arturo Ortín-Martínez, Mostafa Ibrahimi, Nenad T. Pokrajac, Lacrimioara Comanita, Marek Pacal, Mengjia Huang, Shuzo Sugita, Rod Bremner, Valerie A. Wallace · 发表于：Proceedings of the National Academy of Sciences · 年份：2023 · DOI：10.1073/pnas.2308204120 · 被引用次数：5 · 研究领域：Retinal Development and Disorders、Photoreceptor and optogenetics research、Neurogenesis and neuroplasticity mechanisms

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, Crx and SNARE-dependent synaptic function are essential. Thus, both non-cell and cell autonomous mechanisms underpin PR soma sublaminar positioning in the mammalian retina.