Normal brain development requires coordinated cell movements at precise times. It has long been established that cell-cell adhesion proteins of the cadherin superfamily are involved in the adhesion and sorting of cells during tissue morphogenesis. In the present review, we focus on protocadherins, which form the largest subfamily of the cadherin superfamily and mediate homophilic cell-cell adhesion in the developing brain. These molecules are highly expressed during neural development and the exact roles that they play are still emerging. Although, historically, protocadherins were considered to provide mechanical and chemical connections between adjacent cells, recent research suggests that they may also serve as molecular identity markers of neurones to help guide cell recognition and sorting, cell migration, outgrowth of neuronal processes, and synapse formation. This phenomenon of single cell diversity stems, in part, from the vast variation in protein structure, genomic organisation and molecular function of the protocadherins. Although expression profiles and genetic manipulations have provided evidence for the role of protocadherins in the developing brain, we have only begun to construct a complete understanding of protocadherin function. We examine our current understanding of how protocadherins influence brain development and discuss the possible roles for this large superfamily within the hypothalamus. We conclude that further research into these underappreciated but vitally important genes will shed insight into hypothalamic development and perhaps the underlying aetiology of neuroendocrine disorders.
Keywords: cadherins; cell-cell adhesion; hypothalamus; neural development; protocadherins.
© 2015 British Society for Neuroendocrinology.