Development and regeneration of the vertebrate brain

Abstract

The vertebrate brain is hierarchically assembled about orthogonal axes using organizing centers that control cascades of signaling events. The reiterative generation of these centers at defined times, and in precise spatial locations, leads to the conversion of a contiguous and homogenous epithelial sheet into the most complex biological tissue in the animal kingdom. The critical events orchestrating the construction of a "typical" vertebrate brain are described. Attention is focused on specification of major brain regions common across the vertebrate phylogeny, rather than on the differentiation of constituent cell types and specific cytoarchitectures. By uncloaking the complex spatial interactions that unfold temporally during the build of the vertebrate brain, it becomes clear why regeneration of this tissue following injury is such a challenging task. And yet, while mammalian brains fail to regenerate, the brains of non-mammalian vertebrates, such as teleosts, reptiles and amphibians, can successfully reconstitute brain tissue following traumatic injury. Understanding the molecular and cellular bases of this remarkable regenerative capacity is revealing the importance of developmental programs, as well as exposing unexpected roles for extraneous processes such as inflammation. Recent discoveries are now fuelling hope for future therapeutic approaches that will ameliorate the debilitating consequences of brain injury in humans.