Neural patterning in the vertebrate embryo.

The embryonic central nervous system (CNS) is patterned along its antero-posterior, dorsal-ventral, and left-right axes. Along the dorsal-ventral axis, cell fate determination occurs during and following neural tube closure and involves the action of two opposing signaling pathways: SHH ventrally from the notochord and BMP/GDF dorsally from the boundary of neural and nonneural ectoderm and later from the roof plate. In addition, Wnt and retinoic acid signaling have been shown to act in dorsal-ventral patterning; however, their roles are understood in less detail. Along the antero-posterior axis, signals divide the neural tube into four major divisions: forebrain, midbrain, hindbrain, and spinal cord, and these differences can be detected soon after the formation of the neural plate. The FGF, Wnt, and retinoic acid signaling pathways have been implicated in the caudalization of neural tissue. Boundaries of Hox gene expression are observed along the anteroposterior axis and have been suggested to be involved in establishing different identities in the hindbrain and spinal cord. Complex gene expression patterns in the brain suggest the development of neuromeres dividing the brain into different regions that are elaborated further during development. Patterning along the left-right axis occurs concurrently with antero-posterior and dorsal-ventral patterning during gastrulation. A leading candidate for initiating asymmetry is activin, which acts through Nodal and Lefty before any morphological differences are observed. The big challenge will be understanding how these diverse signaling pathways interact both temporally and spatially to generate the complex adult nervous system.