SPECIFICATION OF PITUITARY CELL LINEAGES BY THE LIM HOMEOBOX GENE LHX3

During pituitary organogenesis, the progressive differentiation of dis tinct pituitary-specific cell lineages from a common primordium involv es a series of developmental decisions and inductive interactions. Tar geted gene disruption in mice showed that Lhx3, a LIM homeobox gene ex pressed in the pituitary throughout development, is essential for diff erentiation and proliferation of pituitary cell lineages, In mice homo zygous for the Lhx3 mutation, Rathke's pouch formed but failed to grow and differentiate; such mice lacked both the anterior and intermediat e robes of the pituitary. The determination of all pituitary cell line ages, except the corticotrophs, was affected, suggesting that a distin ct, Lhx3-independent ontogenetic pathway exists for the initial specif ication of this lineage.