*** 9513976 Sive The goals of this proposal are to analyze the mechanisms by which the anteropostenor axis is formed in the ectodenn of the frog Xenopus laevis. The dorsal ectoderm gives rise to all neural tissue and to the non-neural anterior cement gland. Firstly, Dr. Sive will ask whether the homeodomain gene otx2 controls cement gland formation. She isolated otx2 as a product of a subtractive cloning screen for early dorsal ectodermal markers. otx2 misexpression leads to ectopic expression of neural, mesodermal and cement gland genes. otx2 is expressed in the cement gland, making it a good candidate for a primary regulator of cement gland development. Using a hormone-inducible otx2 protein that she constructed, Dr. Sive will ask whether cement gland formation is a direct consequence of otx2 activity. She will also ablate otx2 function by employing antisense ribozymes and body injection. Secondly, she will analyze the mechanisms that restrict expression of a cement gland marker, XAG, to the front of the embryo. Dr. Sive has isolated the XAG promoter, and will analyze the DNA sequence elements and factors that regulate it. Since otx2 may directly activate XAG, she will ask whether otx2 binding sites are present in the XAG promoter. This research will lead to greater understanding of events required for normal neurogenesis, for determining the molecular basis of embryonic neural defects and for defining parameters required for correcting neural lesions neonatally and after trauma or disease later in life. ***
