Posttranslational Mechanisms Control the Timing of bHLH Function and Regulate Retinal Cell Fate

• Published in: Neuron (Cambridge, Mass.) Mass.), 2002-04, Vol.34 (2), p.183-195
• Main Authors: Moore, Kathryn B., Schneider, Meredith L., Vetter, Monica L.
• Format: Article
• Language: English
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors; Calcium-Calmodulin-Dependent Protein Kinases - pharmacology; Cell Differentiation - physiology; Confidence intervals; Deoxyribonucleic acid; DNA; DNA-Binding Proteins - physiology; Drug Resistance; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - physiology; Eye Proteins - antagonists & inhibitors; Eye Proteins - pharmacology; Eye Proteins - physiology; Female; Genes; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; Kinases; Membrane Proteins - drug effects; Membrane Proteins - pharmacology; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - physiology; Nervous System - embryology; NeuroD protein; Neurogenesis; Neurons; Neurosciences; Notch protein; Protein Processing, Post-Translational; Receptors, Notch; Retina; Retina - cytology; Retina - drug effects; Retina - embryology; Retinal Ganglion Cells - cytology; Time Factors; Transcription factors; Transcription Factors - antagonists & inhibitors; Transcription Factors - pharmacology; Transcription Factors - physiology; Xath5 protein; Xenopus; Xenopus laevis - embryology; Xenopus Proteins; XNeuroD protein
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(02)00666-9

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 posttranslationally, so that bHLH factors with overlapping expression can function independently. Specifically, XNeuroD function in the retina can be inhibited by glycogen synthase kinase 3β (GSK3β), 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.