Identification of members of the Wnt signaling pathway in the embryonic pituitary gland

Prop1 is one of several transcription factors important for the development of the pituitary gland. Downstream targets of PROP1 and other critical pit uitary transcription factors remain largely unknown. We have generated a pa rtial expression profile of the developing pituitary gland containing over 350 transcripts, using cDNA subtractive hybridization between Prop1(df/df) and wild-type embryonic pituitary gland primordia. Numerous classes of gene s including transcription factors, membrane associated molecules, and cell cycle regulators were identified in this study. Of the transcripts, 34% do not have sequence similarity to known genes, but are similar to ESTs, and 4 % represent novel sequences. Pituitary gland expression of a number of clon es was verified using in situ hybridization. Several members of the Wnt signaling pathway were identified in the develop ing pituitary gland. The frizzled2 receptor, Ape, beta -catenin, groucho, a nd a novel isoform of TCF4 (officially named Tcf712) were identified in dev eloping pituitary libraries. Three N-terminal alternatively spliced Tcf712 isoforms are reported here, each of which lacks a DNA-binding domain. Funct ional studies indicate that these isoforms can act as endogenous inhibitors of Win signaling in some contexts. This is the first report of Tcf712 and Fzd2 expression in the developing pi tuitary. These molecules may be important in mediating Wnt signaling during pituitary ontogeny. We expect other transcripts from these libraries to be involved in pituitary gland development.