Posttranslational mechanisms control the timing of bHLH function and regulate retinal cell fate

During central nervous system development, neurons are often born in a precise temporal sequence. Basic helix-loop-helix (bHLH) transcription factors are required for the development of specific subpopulations of neurons, but how they contribute to their ordered genesis is unclear. We show that the ability of bHLH factors to regulate the development of distinct neuronal subtypes in the Xenopus retina depends upon the timing of their function. In addition, we find that the timing of bHLH function can be regulated post-translationally, so that bHLH factors with overlapping expression can function independently. Specifically, XNeuroD function in the retina can be inhibited by glycogen synthase kinase 3beta (GSK3beta), while Xath5 function can be inhibited by Notch. Thus, the potential of bHLH factors to regulate the development of neuronal subtypes depends upon the context in which they function.