NSF Award
0321878
0321878<br/>Sive<br/><br/>This proposal focuses on the mechanism by which an organ is positioned during embryonic development. The extreme front ("anterior") of embryos of the frog Xenopus will be studied, with focus on two organs, the cement gland and the stomodeum. The cement gland is a simple mucus-secreting cell layer that "glues" the newly hatched embryo to a solid support. It derives from the outer layer of the embryonic ectoderm. The stomodeum derives from the inner layer of the ectoderm and forms part of the primitive mouth. Experimental data has been incorporated into a "Venn diagram model" which suggests that overlap of three domains of gene activity positions the cement gland/stomodeal region. These are an anterodorsal (AD) domain, a ventrolateral domain (VL) and an outer (EO) or inner ectodermal (EI) domain. It is proposed that AD + VL + EO = cement gland, and that AD + VL+ EI = stomodeum. The goals of this proposal are firstly, to further test the Venn diagram model by connecting the decision to make a cement gland ("determination") with the final form and function of the organ ("differentiation"). The activity of four genes (c-jun and three Ets family members) that may regulate expression of the cement gland marker, Xag1 will be tested in gain and loss of function assays. Possible parallel pathways of cement gland determination will be analyzed by examining the gob4 promoter. Secondly, stomodeum and cement gland formation will be compared. Genes in the AD and VL domains, that control cement gland formation, will be tested for their role in stomodeum formation. <br/><br/>The proposal has the intellectual merit of asking how the mouth region is positioned. This important region of the embryo is poorly understood. Both the cement gland and primitive mouth are relatively simple organs, which present unusual opportunities to study the complete time course of organ formation. Multiple familial deformities of mouth development are known, and this proposal has the broad impact of helping to clarify genetic causes of these birth defects. In addition, the P.I. is committed to education at all levels, and the proposal has further broad impact in the following ways. Several, individuals working on this project will receive training in scientific method, which will promote their future careers. A new edition of a laboratory manual describing the care and use of Xenopus will be prepared during this project, and will impact members of the community in their use of the Xenopus model.
