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 posttranslationally, 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.
Moore
Kathryn B
KB
Department of Neurobiology and Anatomy, University of Utah, 20 North 1900 East, Salt Lake City, UT 84132, USA.
Schneider
Meredith L
ML
Vetter
Monica L
ML
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D004351:Drug Resistance; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D005260:Female; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D008565:Membrane Proteins / Q000187:drug effects / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009420:Nervous System / Q000196:embryology; D011499:Protein Processing, Post-Translational; D051880:Receptors, Notch; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology; D013997:Time Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology
D051792:Basic Helix-Loop-Helix Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; D029867:Xenopus Proteins; C109416:ATOH7 protein, Xenopus; C093564:Neurogenic differentiation factor 1