NeuroD: the predicted and the surprising.
NeuroD (otherwise known as BETA2) is a basic helix-loop-helix (bHLH) transcription factor that is capable of converting embryonic epidermal cells into fully differentiated neurons in Xenopus embryos. In insulinoma cells, NeuroD can bind and activate the insulin promoter. When NeuroD is deleted in mice, the early differentiating pancreatic endocrine cells and a subset of the neurons in the central and peripheral nervous systems die, resulting in cellular deficits in the pancreatic islets, cerebellum, hippocampus and inner ear sensory ganglia. As a consequence, mice become diabetic and display neurological defects including ataxia and deafness. These gain-of-function and loss-of-function phenotypes suggest that NeuroD controls both common and distinct sets of molecules involved in cell survival and differentiation in different tissue types. In this review, we examine what is known about NeuroD and what remains to be answered. Understanding the primary function of NeuroD will be extremely valuable in the diagnosis and cure of the diseases that involve this transcription factor, which plays essential roles in the development and function of the pancreas and the nervous system.
Chae
Ji Hyung
JH
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347, USA.
Stein
Gretchen H
GH
Lee
Jacqueline E
JE
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D003920:Diabetes Mellitus / Q000235:genetics; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006801:Humans; D007340:Insulinoma / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D009420:Nervous System / Q000196:embryology; D009474:Neurons / Q000378:metabolism; D010179:Pancreas / Q000196:embryology; D010641:Phenotype; D017434:Protein Structure, Tertiary; D014981:Xenopus
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C093564:Neurogenic differentiation factor 1