Math5 is required for retinal ganglion cell and optic nerve formation
Author:
Brown Nadean L.12, Patel Sima2, Brzezinski Joseph1, Glaser Tom1
Affiliation:
1. Departments of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, MI 48109-0650, USA 2. Department of Pediatrics at Children’s Memorial Institute for Education and Research, Northwestern University Medical School, Chicago, IL 60614-3394, USA
Abstract
The vertebrate retina contains seven major neuronal and glial cell types in an interconnected network that collects, processes and sends visual signals through the optic nerve to the brain. Retinal neuron differentiation is thought to require both intrinsic and extrinsic factors, yet few intrinsic gene products have been identified that direct this process. Math5 (Atoh7) encodes a basic helix-loop-helix (bHLH) transcription factor that is specifically expressed by mouse retinal progenitors. Math5 is highly homologous to atonal, which is critically required for R8 neuron formation during Drosophila eye development. Like R8 cells in the fly eye, retinal ganglion cells (RGCs) are the first neurons in the vertebrate eye. Here we show that Math5 mutant mice are fully viable, yet lack RGCs and optic nerves. Thus, two evolutionarily diverse eye types require atonal gene family function for the earliest stages of retinal neuron formation. At the same time, the abundance of cone photoreceptors is significantly increased in Math5−/− retinae, suggesting a binary change in cell fate from RGCs to cones. A small number of nascent RGCs are detected during embryogenesis, but these fail to develop further, suggesting that committed RGCs may also require Math5 function.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
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