Dorsal-ventral patterning of the neural tube: a tale of three signals

Development of the vertebrate nervous system begins with the acquisition of neural identity from the midline dorsal-ectodermal cells of the gastrulating embryos. The subsequent progressive specification of the neural plate along its anterior-posterior and dorsal-ventral (DV) axes allows the generation of the tremendous variety of neuronal and glial cells that compose the vertebrate central nervous system (CNS). Studies on the development of the spinal cord, the anatomically simplest part of the CNS, have generated most of our current knowledge on the signaling events and the genetic networks that orchestrate the DV patterning of the neural plate. In this review, we discuss the recent advances in our understanding of these events and highlight unresolved questions. We focused our attention on the activity and the integration of the three main instructive cues: Sonic hedgehog, the Wnts and the Bone Morphogenetic Proteins, giving particular attention to the less well understood dorsal signaling events.