Role of the Bicoid-related homeodomain factor Pitx1 in specifying hindlimb morphogenesis and pituitary development.
Pitx1 is a Bicoid-related homeodomain factor that exhibits preferential expression in the hindlimb, as well as expression in the developing anterior pituitary gland and first branchial arch. Here, we report that Pitx1 gene-deleted mice exhibit striking abnormalities in morphogenesis and growth of the hindlimb, resulting in a limb that exhibits structural changes in tibia and fibula as well as patterning alterations in patella and proximal tarsus, to more closely resemble the corresponding forelimb structures. Deletion of the Pitx1 locus results in decreased distal expression of the hindlimb-specific marker, the T-box factor, Tbx4. On the basis of similar expression patterns in chick, targeted misexpression of chick Pitx1 in the developing wing bud causes the resulting limb to assume altered digit number and morphogenesis, with Tbx4 induction. We hypothesize that Pitx1 serves to critically modulate morphogenesis, growth, and potential patterning of a specific hindlimb region, serving as a component of the morphological and growth distinctions in forelimb and hindlimb identity. Pitx1 gene-deleted mice also exhibit reciprocal abnormalities of two ventral and one dorsal anterior pituitary cell types, presumably on the basis of its synergistic functions with other transcription factors, and defects in the derivatives of the first branchial arch, including cleft palate, suggesting a proliferative defect in these organs analogous to that observed in the hindlimb.
Szeto
D P
DP
Howard Hughes Medical Institute, University of California, San Diego, School and Department of Medicine, La Jolla, California 92093-0648, USA.
Rodriguez-Esteban
C
C
Ryan
A K
AK
O'Connell
S M
SM
Liu
F
F
Kioussi
C
C
Gleiberman
A S
AS
Izpisúa-Belmonte
J C
JC
Rosenfeld
M G
MG
D000818:Animals; D030161:Avian Proteins; D001934:Branchial Region / Q000196:embryology / Q000254:growth & development; D002642:Chick Embryo; D029721:Drosophila Proteins; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006614:Hindlimb / Q000196:embryology / Q000254:growth & development*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008334:Mandible / Q000196:embryology / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics*; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D010902:Pituitary Gland / Q000196:embryology / Q000254:growth & development*; D020825:T-Box Domain Proteins; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014921:Wings, Animal / Q000196:embryology / Q000254:growth & development*; D000097577:Homeobox Protein PITX2
D030161:Avian Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D051761:Paired Box Transcription Factors; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C491196:TBX4 protein, Gallus gallus; C103177:Tbx4 protein, mouse; C056478:bcd protein, Drosophila; C101485:homeobox protein PITX1; C433629:homeobox protein PITX3