Affiliation:
1. Developmental Neurobiology Unit, Okinawa Institute of Science and Technology Graduate University
Abstract
In the vertebrate retina, an interplay between retinal ganglion cells (RGCs), amacrine (AC), and bipolar (BP) cells establishes a synaptic layer called the inner plexiform layer (IPL). This circuit conveys signals from photoreceptors to visual centers in the brain. However, the molecular mechanisms involved in its development remain poorly understood. Striatin-interacting protein 1 (Strip1) is a core component of the striatin-interacting phosphatases and kinases (STRIPAK) complex, and it has shown emerging roles in embryonic morphogenesis. Here, we uncover the importance of Strip1 in inner retina development. Using zebrafish, we show that loss of Strip1 causes defects in IPL formation. In strip1 mutants, RGCs undergo dramatic cell death shortly after birth. AC and BP cells subsequently invade the degenerating RGC layer, leading to a disorganized IPL. Mechanistically, zebrafish Strip1 interacts with its STRIPAK partner, Striatin 3 (Strn3), and both show overlapping functions in RGC survival. Furthermore, loss of Strip1 or Strn3 leads to activation of the proapoptotic marker, Jun, within RGCs, and Jun knockdown rescues RGC survival in strip1 mutants. In addition to its function in RGC maintenance, Strip1 is required for RGC dendritic patterning, which likely contributes to proper IPL formation. Taken together, we propose that a series of Strip1-mediated regulatory events coordinates inner retinal circuit formation by maintaining RGCs during development, which ensures proper positioning and neurite patterning of inner retinal neurons.
Funder
Okinawa Institute of Science and Technology Graduate University
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Reference115 articles.
1. The molecular basis of retinal ganglion cell death in glaucoma;Almasieh;Progress in Retinal and Eye Research,2012
2. Neuronal Migration and Lamination in the Vertebrate Retina;Amini;Frontiers in Neuroscience,2017
3. FastQC: A Quality Control Tool for High Throughput Sequence Data;Andrews,2010
4. Anti-apoptotic BCL-2 family proteins in acute neural injury;Anilkumar;Frontiers in Cellular Neuroscience,2014
5. Analysis of the retina in the zebrafish model;Avanesov;Methods in Cell Biology,2010
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献