Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia.
Deficiencies in the homeobox transcription factors LHX4 and PROP1 cause pituitary hormone deficiency in both humans and mice. Lhx4 and Prop1 mutants exhibit severe anterior pituitary hypoplasia resulting from limited differentiation and expansion of most specialized cell types. Little is known about the mechanism through which these genes promote pituitary development. In this study we determined that the hypoplasia in Lhx4 mutants results from increased cell death and that the reduced differentiation is attributable to a temporal shift in Lhx3 activation. In contrast, Prop1 mutants exhibit normal cell proliferation and cell survival but show evidence of defective dorsal-ventral patterning. Molecular genetic analyses reveal that Lhx4 and Prop1 have overlapping functions in early pituitary development. Double mutants exhibit delayed corticotrope specification and complete failure of all other anterior pituitary cell types to differentiate. Thus, Lhx4 and Prop1 have critical, but mechanistically different roles in specification and expansion of specialized anterior pituitary cells.
Department of Human Genetics and. Graduate Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0638, USA.
Lori T
LT
Raetzman
Robert
R
Ward
Sally A
SA
Camper
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019521:Body Patterning / Q000502:physiology*; D002470:Cell Survival; D004392:Dwarfism / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics; D010902:Pituitary Gland / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C108538:Lhx4 protein, mouse; D009419:Nerve Tissue Proteins; C102134:Prophet of Pit-1 protein; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1