Expression and regulation of Pitx genes during vertebrate organogenesis
Description
Pitx1 and Pitx2 define a new family of bicoid related homeobox genes. The respective expression patterns of these two genes suggests their importance during vertebrate embryo development. Of particular interest is the expression and regulation of these genes during murine tooth development. The expression patterns of both Pitx1 and Pitx2 in the tooth forming region as well as the tooth defect found in patients with Rieger syndrome suggest that both Pitx1 and Pitx2 play a role in the early stages of odontogenesis. Studies show that overlapping domains of Fgf8 and Bmp4 signaling regulate the expression of both Pitx1 and Pitx2 in the tooth forming region Since Pitx2 is an early marker for the dental epithelium, the chicken homologue of Pitx2 (cPitx2) was cloned in an effort to search for molecular markers for the presumptive tooth germ in Aves. Interestingly, in addition to the expression of this gene in the chick mandible, cPitx2 was also asymmetrically expressed relative to the left-right axis of the developing embryo. Studies show that regulation of this gene in the left-lateral plate mesoderm is regulated by the well documented shh-nodal pathway. In addition, expression of cPitx2 in the left half of the fused heart tube appears to be regulated by retinoic acid as demonstrated by the reduced expression of cPitx2 in vitamin A-deficient quail embryos. Finally, upon cloning the chicken homologue of Pitx2 , two isoforms of this gene were isolated, isoform A (cPitx2A ) and isoform B (cPitx2B). However, Northern blot analyses indicates that at least 3, possibly more, isoforms are expressed and may correspond to the various expression patterns of cPitx2 throughout embryogenesis. The expression of antisense cPitx2 transcripts was also detected. The presence of antisense cPitx2 transcripts through development in vivo, as confirmed by Northern blot and RNase Protection Assay (RPA) analysis, suggest yet another mechanism for the regulation of cPitx2 activity. The complementary expression pattern of sense and antisense cPitx2 in the endothelial and hematopoietic cells of the embryonic vasculature, respectively, suggest that these two genes may be involved in regulating the differentiation of the endothelial and hematopoietic cell lineages respectively