Regulation of Math5
During retinal neurogenesis the staggered onset of bHLH factor expression correlates with the neuronal birthdates of particular neuron classes. Little is known about the regulation of these genes, particularly their temporal control that instructs retinal progenitors to distinct fates. One obvious candidate to regulate retinal fates is the transcription factor Pax6. All developing eye cells express Pax6 at some stage, and the removal of Pax6 function causes a complete failure of eye development. Two retinal bHLH proteins, Math5 and Hes1, require Pax6 in a dosage-sensitive manner, suggesting they are downstream targets. If Pax6 activates Math5 transcription, what controls their offset temporal expression? Precise temporal expression must be inherent to bHLH function because the times when progenitors express each gene influences their neuronal subtype at differentiation.
Similarly, spatial regulation is critical since vertebrate retinogenesis proceeds either from central to peripheral (amniotes) or ventronasal to dorsotemporal (anamniotes). Pax6 is unlikely the sole regulator of Math5, since optic cup cells uniformly express Pax6 at the time of Math5 patterning. One potential temporal regulator of proneural bHLHs is Hes1, a transcriptional repressor of neurogenesis and gliogenesis. For an initial survey of Math5 regulatory regions, we constructed a series of transgenes containing different 5' or 3' conserved sequences of Math5 genomic DNA driving a jellyfish green fluorescent protein (GFP) reporter. The analysis of Math5 regulation using these transgenics is currently a major focus of research in the lab.
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).
