Keeping tab on NeuroD

Ji-Hyung Chae¹, Chris Dufton¹, Dado Marcora², and Jacqueline E. Lee¹

¹Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309; ² Current address: California Institute of Technology, Division of Biology, Pasadena, CA 91125

NeuroD, otherwise known as BETA2, is a potent basic helix-loop-helix (bHLH) transcriptional factor capable of converting embryonic epidermal fate into neuronal fate in Xenopus embryos.  In mice, NeuroD is required for a proper development of the granule cells of the cerebellum and hippocampus, sensory ganglia of the inner ear, and endocrine cells of the pancreas.  In mice lacking NeuroD, these cells undergo cell death shortly after exiting cell cycle.  Consequently, NeuroD-null mice are severely ataxic, deaf, and diabetic. Recent molecular and functional analyses of NeuroD revealed that NeuroD is regulated at the transcriptional, post-transcriptional, and post-translational levels.  In addition, protein-protein interaction between NeuroD and Mixed Lineage Kinase 2 (MLK2) and Huntingtin-Associated Protein 1 (HAP1) can stimulate the neurogenic activity of NeuroD. We hypothesize that different modes of regulation are used to control the function of NeuroD in a spatiotemporal manner and that they play important roles not only during development, but also in mature cells for the maintenance of homeostasis.  Current data and future experiments to address our hypothesis will be discussed.