Developmental Neurobiology: to better understand the mechanisms controlling the early pattern of the developing nervous system; the processes of neurogenesis, axonal guidance, and neural crest differentiation
Supporting basic research that contributes to our understanding of how the nervous system develops under both normal and abnormal conditions is the major focus of the Developmental Neurobiology Program. Many structural neurological birth defects are caused by problems during early neural development. Formation of the nervous system begins shortly after gastrulation, when the cells of the dorsal ectoderm are induced by the underlying mesoderm to become the neural plate that extends the length of the embryo. From this very simple neural plate, convergence and extension morphogenetic activities begin a process, which ultimately results in a highly stereotyped, complex, and integrated nervous system. During neurulation, the neural tube is formed, and the embryonic nervous system is patterned along the three major axes. Neural progenitor cells and their offspring derive positional information from within these boundaries; neurons and glia are generated, and acquire specific cell fates. The diversity of cell types that make up the adult system is generated from this undifferentiated neuroepithelium. These new cells migrate to specific positions within the developing nervous system and send out processes to specific targets. Once specific patterns of connectivity are generated, synapses are formed, and hormonal and trophic factors influence the survival, differentiation and selective elimination of these connections.
Goals are to understand the mechanisms that control nervous system formation—that is, to:
- Elucidate the morphogenetic and regulatory processes associated with neural tube formation;
- Determine how nerve call progenitors divide, migrate and begin to differentiate into specific types of nerve cells;
- Understand path finding strategies of immature, developing neurons so that they get to the correct location and make appropriate connection with their targets;
- Decipher how synapses between appropriate targets form; and
- Understand how superfluous synapses and neurons are eliminated.
While embryonic development of the nervous system remains a complex process, recent advances in genetics, genomics, and proteomics now allow for a more in-depth analysis of the processes underlying its development. In addition, genes, genetic networks, and the timing of their activation and inactivation are also conserved, in large part, across species, making it possible to predict some of the underlying mechanisms of human development based on studies that use animal models. With newly developed tools, investigators are now better able to examine the underlying mechanisms of neural development and are learning that similar developmental strategies are used multiple times during nervous system development. One area of specific interest to the Branch involves neural tube closure and the resultant birth defects that occur when this process is compromised.