Emergence of distinct cell types from a common primordium during pituitary development occurs in response to opposing signaling gradients that induce an overlapping temporal and spatial pattern of transcriptional regulators. Opposing actions of two structurally related DNA-binding transcription factors direct early and late developmental events by sequentially repressing and activating an overlapping set of target genes. Complementary genetic and genomic approaches will now permit a full elucidation of the precise molecular mechanisms that underlie all phases of pituitary organogenesis.

Genetic, molecular biological, and more recently genomic approaches have permitted over the last 25 yr a revealing outline of events that underlie embryogenesis, including the generation of organs containing distinct cell types from common primordia. These investigations have consistently revealed the critical role of spatially expressed signals and gradients of signaling molecules in establishing positional commitment events, based on induction of cohorts of transcription factors that control subsets of genes that specify cell type determination, and subsequently, differentiation. Cellautonomous commitment is often correlated with establishment of autoregulatory loops of restricted, often cell typespecific transcription factors. The developing pituitary gland is an instructive model system for investigating the transcriptional control of patterning and cell type specification because its maturation involves a series of distinct stages that generate from a common population of ectodermal progenitors a complex organ composed of six well-defined hormone-producing cell types. The murine pituitary primordium is defined at an intimate point of contact between the neural ectoderm and the oral roof ectoderm on embryonic d 8.5 (E8. 5) that marks the first event in development of the pituitary (48). These two embryonic components ultimately produce a three-lobed gland: one part neurohypophysis, the posterior lobe that contains the axonal projections from the hypothalamus, and two parts adenohypophysis, the anterior and intermediate lobes that are composed of the hormone-secreting cell types. Recent studies have demonstrated that patterning of the anterior pituitary emerges through the influence of sequential, opposing signaling gradients, which induce temporally and spatially specific domains of transcription factor expression. The combinatorial distribution of these transcription factors dorsally/ventrally and rostrally/caudally directs cell lineage fate and final differentiation as a gonadotrope (producing FSH and LH), a thyrotrope (producing TSH), a somatotrope