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 neuron's 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-, 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.
Dr. Bradley and colleagues have discovered that that although the Pcdh gene clusters share a similar genomic structure to the immunoglobin genes in the immune system -- where antibody protein diversity confers antigen-binding specificity -- the neuron-specific expression of Pcdh proteins is accomplished by an entirely different mechanism.
As Dr. Bradley explains, "We tested the various models by creating mice with a variety of modified allele
'"/>
Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
31-Jul-2002