Migrating into Genomics with the Neural Crest

Neural crest cells are a fascinating embryonic cell type, unique to vertebrates, which arise within the central nervous system but emigrate soon after its formation and migrate to numerous and sometimes distant locations in the periphery. Following their migratory phase, they differentiate into diverse derivatives ranging from peripheral neurons and glia to skin melanocytes and craniofacial cartilage and bone. The molecular underpinnings underlying initial induction of prospective neural crest cells at the neural plate border to their migration and differentiation have been modeled in the form of a putative gene regulatory network. This review describes experiments performed in my laboratory in the past few years aimed to test and elaborate this gene regulatory network from both an embryonic and evolutionary perspective. The rapid advances in genomic technology in the last decade have greatly expanded our knowledge of important transcriptional inputs and epigenetic influences on neural crest development. The results reveal new players and new connections in the neural crest gene regulatory network and suggest that it has an ancient origin at the base of the vertebrate tree. 1. Introduction The neural crest is an embryonic cell population characterized by its multipotency, extensive migratory ability, and capacity to form multiple and diverse derivatives [1]. Initially arising within the developing central nervous system (CNS) of vertebrate embryos, these cells depart from the CNS by undergoing an epithelial to mesenchymal transition (EMT) similar to that undertaken by cancer cells during metastasis [2]. Neural crest cells invade the periphery, migrating along characteristic pathways to diverse locations where they differentiate into numerous derivatives. Just as the CNS is regionalized along the neural axis to form the brain in the anterior portion of the body and the spinal cord in trunk region, the neural crest can also be subdivided into different populations along the body axis [1] which form some overlapping as well as some divergent derivatives (Figure 1). Cranial neural crest cells arise in the head region of the embryo. In the chick embryo, on which this review focuses, they migrate from the forebrain/midbrain as a large swathe of cells which expands like a cobra’s hood. At the level of the hindbrain, however, they migrate in segmental streams to populate elements of the facial skeleton, including the upper and lower jaw as well as bones of the neck. Other cranial crest cells contribute to all of the glia and some neurons of cranial sensory