Brief Activity of Proneural Proteins Critical to Normal Neurogenesis Is Regulated by Reversible Phosphorylation of Highly Conserved Region in These Proteins

Dr. Bassem Hassan’s team at the VIB Center for the Biology of Disease in Leuven, Belgium, together with international colleagues, has discovered a previously unknown mechanism that is highly conserved between and among species, and that regulates neurogenesis through precise temporal control of the activity of a small family of proteins essential for brain development: namely, the proneural proteins. This newly described mechanism, a simple reversible phosphorylation of a highly conserved region in proneural proteins, is critical for the production of a sufficient number of neurons, their differentiation, and the development of the nervous system. The discovery of this critically important mechanism was reported in the January 28, 2016 issue of the prestigious journal Cell. The Cell article is titled “Post-Translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis.” One of the senior authors of the article is Dr. Huda Zoghbi of the Baylor College of Medicine. Our nervous system is made up of an astonishing diversity of neurons. And yet, only a very small number of proteins are needed to generate and determine the identity of these billions of neurons. An even smaller number of proteins, called proneural proteins, initiate and regulate brain development and neurogenesis (i.e., the manufacture of functional neurons from neural stem cells). These proneural proteins are transcription factors, meaning that they control the expression of other proteins by regulating the transcription of DNA to mRNA. Proneural proteins are expressed very transiently during early neurogenesis. A key aspect of this system, which remains to be elucidated, is the precise temporal regulation of the activity of the proneural proteins and the manner in which this regulation contributes to neural differentiation.
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