PITUITARY LINEAGE DETERMINATION BY THE PROPHET OF PIT-1 HOMEODOMAIN FACTOR DEFECTIVE IN AMES DWARFISM

The gene apparently responsible for a heritable form of murine pituita ry-dependent dwarfism (Ames dwarf, df) has been positionally cloned, i dentifying a novel, tissue-specific, paired-like homeodomain transcrip tion factor, termed Prophet of Pit-1 (Prop-1). The df phenotype result s from an apparent failure of initial determination of the Pit-1 linea ge required for production of growth hormone, prolactin or thyroid-sti mulating hormone, resulting in dysmorphogenesis and failure to activat e Pit-1 gene expression. These results imply that a cascade of tissue- specific regulators is responsible for the determination and different iation of specific cell lineages in pituitary organogenesis.