Scientists from Baylor College of Medicine (Texas, USA) and the Wellcome Trust Sanger Institute (Cambridge, UK) have deciphered how neurons can synthesize a diverse range of proteins from a relatively limited number of genes – a discovery with important implications for understanding how complex neural circuitry is formed and maintained throughout our lives.
A long-standing question in neurobiology is how each of the tens of thousands of neurons that populate the mammalian brain are instructed to establish the specific connections that give rise to our complex neural networks. Researchers postulate that the expression of distinct sets of proteins in each individual neuron act as molecular cues to direct the course of each neurons fate. The protocadherin (Pcdh) family of proteins are prime candidates for this job, as each individual neuron expresses an overlapping but distinct combination of Pcdh proteins.
In the August 1 issue of Genes & Development, Dr. Allan Bradley and colleagues report on their identification of the mechanism of neuron-specific Pcdh expression. The Pcdh family of proteins is encoded by three gene clusters (Pcdh-a, Pcdh-ß, and Pcdh-g) on human chromosome #5, and mouse chromosome #18. The a and g clusters each contain genes with several variable exons (coding regions of DNA). Each variable exon can be separately joined to a constant region of the gene, thereby creating the genetic blueprint for a Pcdh protein that will have a unique variable region and a common constant region.
Heather Cosel | EurekAlert!
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