PTX1, A BICOID-RELATED HOMEO BOX TRANSCRIPTION FACTOR INVOLVED IN TRANSCRIPTION OF THE PROOPIOMELANOCORTIN GENE

The pituitary gland contains six distinct hormone-producing cell types that arise sequentially during organogenesis. The first cells to diff erentiate are those that express the pro-opiomelanocortin (POMC) gene in the anterior pituitary lobe. The other lineages, which appear later , include cells that are dependent on the POU factor Pit-1 and another POMC-expressing lineage in the intermediate pituitary lobe. Using AtT -20 cells as a model for early expression of POMC in the anterior pitu itary, we have defined a regulatory element conferring cell specificit y of transcription and cloned a cognate transcription factor. This fac tor, Ptx1 (pituitary homeo box 1), contains a homeo box related to tho se of the anterior-specific genes bicoid and orthodenticle in Drosophi la, and Otx-1 and Otx-2 in mammals. Ptx1 activates transcription upon binding a sequence related to the Drosophila bicoid target sites. Ptx1 is the only nuclear factor of this DNA-binding specificity that is de tected in AtT-20 cells, and it is expressed at high levels in a subset of adult anterior pituitary cells that express POMC. However, Ptx1 is expressed in most cells of Rathke's pouch at an early time during pit uitary development and before final differentiation of hormone-produci ng cells. Thus, Ptx1 may have a role in differentiation of pituitary c ells, and its early expression pattern suggests that it may have a rol e in pituitary formation. In the adult pituitary gland, Ptx1 appears t o be recruited for cell-specific transcription of the POMC gene.