The spatially and temporally overlapping processes of gastrulation and neurulation and the concomitant interactions among developing tissues and organ rudiments result in the formation and subsequent patterning of the neuraxis: the neural tube--the rudiment of the entire adult central nervous system--and the associated axial (i.e. notochord) and paraxial (i.e. somites) mesoderm--rudiments of the vertebral column, skeletal muscle and related structures. In the proposed project, the applicant will use avian embryos to address three specific aims. (1) To identify the tissue and cellular basis of gastrulation in higher vertebrates. The applicant's central hypothesis is that morphogenetic movements, constituting the four critical events of gastrulation, are driven by multiple cell behaviors whose relative contributions can be characterized and experimentally evaluated. (2) To continue analyzing the tissue and cellular basis of neurulation in higher vertebrates. The applicant's central hypothesis is that previously identified cell behaviors in the neural plate, epidermis and nascent neural folds are both sufficient and necessary for bending of the neural plate and subsequent closure of the neural groove. (3) To continue elucidating the cellular and molecular microenvironmental signaling that evokes specification, determination, and patterning of ectodermal and mesodermal cells in higher vertebrates. The applicant's central hypothesis is that cell interactions, mediated partially through secreted growth factors, alter the microenvironment and thereby regulate the development of mesodermal and ectodermal components of the neuraxis. Through achieving these specific aims, the proposed project is expected to define key mechanisms that result in the formation and patterning of the neuraxis. The applicant's studies based on extensive preliminary data and substantial progress during the previous project period, examine important questions in developmental neurobiology and utilize several techniques with which the applicant has considerable expertise including whole-embryo culture, microsurgery, tissue grafting, cell labeling, time-lapse microscopy, histology, immunocytochemistry, and whole mount in situ hybridization. The applicant's past results and the new information gained from the proposed studies are expected to form a solid foundation for understanding normal development and provide valuable insight into mechanisms responsible for fetal wastage and common serious birth defects in humans.
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