Initiation of Vertebrate Retinal Neurogenesis
In the vertebrate retina basic helix-loop-helix (bHLH) factors are instructional molecules for retinal neuron formation. Mutations in these genes cause defects in retinal neuron development and function. Yet, very little is known about the genetic regulation or biochemical action of these genes, meaning it is not yet possible to fully explain retinal neuron formation molecularly. The expression of bHLH factors coincides with the onset of specification and differentiation of particular retinal neuron classes (e.g. Math5 and RGCs).
RGCs appear first in the vertebrate retina (Figures 1 and 2). RGC neurons require the Math5 bHLH gene for proper development. In the developing mouse retina, five neuron-promoting bHLH genes have been identified: Math5, Ngn2, Math3, NeuroD and Mash1. The expression of each proneural gene coincides with a peak of genesis for distinct retinal cell type(s) and their activation occurs sequentially, staggered across several days of development (Figure 2). Mutational and ectopic expression experiments have shown that progenitors are biased to particular fates by their expression of one or more bHLH proteins. When optic cup cells expressing Math5, they also express the paired domain factor Pax6 (Figure 3). Because Pax6 expression initiates prior to Math5, it is a good candidate as an upstream regulator.
Contact Us
The Brown laboratory is part of the Division of Developmental Biology and the Department of Ophthalmology at Cincinnati Children's Research Foundation and the University of Cincinnati School of Medicine. Our lab is located in Location R (Research Foundation Building), Room 1455.
Our laboratory participates in pre- and post-doctoral training through the Molecular and Developmental Biology and Neuroscience Programs. Inquiries from interested trainees are always welcome.
For more information, please contact Nadean Brown at 513-636-1963 (nadean.brown@cchmc.org).
