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Vol. 13, No. 4, pp. 484-494, February 15, 1999
1 Howard Hughes Medical Institute, University of
California, San Diego, School and Department of Medicine, La Jolla,
California 92093-0648 USA; 2 The Salk Institute, Gene
Expression Laboratory, La Jolla, California 92037 USA
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.
[Key Words: Pitx1; morphogenesis; hindlimb development; pituitary]
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