A central goal of developmental neurobiology has been to identify molecular controls which determine the final three-dimensional shape of the nervous system and the orderly arrangement of its many cell types. The molecular controls that underlie morphogenesis rely on ever-changing interactions between a cell's microenvironment and its inherited information.Lineage analysis allows targeted searches for these molecular controls.It has done so by: a) revealing potential relationships between inherited information or environmental cues and cell fate and, b) delineating the period in development during which these relationships could be operational. The investigator's objective is to develop a fate map of the avian hypothalamus to identify possible relationships between inherited information and cell type determination, pattern formation and the establishment of functionally important cellular connections. The hypothalamus is ideally suited to permit descriptions of highly specific lineal relationships because of its anatomic and functional compartmentalization as well as characterization of its neurons by specific neuropeptide products. Accurate descriptions of lineage relationships in the hypothalamus will be achieved using a newly developed retroviral approach. Progenitor cells will be infected in vivo with libraries of replication incompetent retrovirus vectors. Each vector encodes both a histochemical marker gene as well as additional sequences that serve as genetic tags. The viral genome is stably integrated into the host genome, and is passed on to all progeny cells, yet appears not to affect development itself. Progeny cells will be identified histochemically. Each virally infected cell will be mapped within the hypothalamus. Clonal relationships will be established by amplifying the genetic tag from each virally infected cell. The location, morphology, cell type and neuropeptide product of each cell in a clone will be described. Identifying recurrent lineal relationships will clarify the potential role of lineage in determining neuronal cell types, nuclear formations and patterns of clonal dispersion. Preliminary data during early development of the hypothalamus have already suggested potentially important relationships between inherited information and three-dimensional patterning of the hypothalamus. The investigator has identified hypothalamic clones that have their cells distributed in exactly symmetrical positions on both the left and right side of the brain. She has postulated that these unusual and rare clones may be derived from specialized midline cells and serve to determine the symmetrical pattern of the hypothalamus. She proposes to extend her lineage analysis into the later part of hypothalamic development when final cell types and nuclear formations can be identified. Identifying the molecular controls of both cell differentiation and specification may provide understanding of normal and abnormal development and may offer the long sought after therapeutic approaches to both central nervous system anomalies and injury.
| Arnold-Aldea, S A; Sterritt, C (1996) Sites of origin and patterns of migration of vasotocin/mesotocin neurons in developing brain of the chick. J Neurobiol 31:103-16 |
