High impact information on Pitx1

• 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 [1].
• Deletion of the Pitx1 locus results in decreased distal expression of the hindlimb-specific marker, the T-box factor, Tbx4 [1].
• Role of the Bicoid-related homeodomain factor Pitx1 in specifying hindlimb morphogenesis and pituitary development [1].
• 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 [1].
• 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 [1].

Biological context of Pitx1

• Recently, increased cell apoptosis in Rathke's pouch has been described in mutant mice impaired in the function of the bicoid-like homeodomain proteins Pitx1 and Pitx2 [2].
• During early mouse embryogenesis, Pitx1 (pituitary homeobox 1), a member of the bicoid subgroup of PAIRED homeobox-containing transcription factors, marks the stomodeum, oral ectoderm, pituitary and first branchial arch in the anterior part of the embryo and lateral plate mesoderm only in the posterior half of the embryo [3].
• Pitx1 in vivo promoter activity and mechanisms of positive autoregulation [3].
• The Pitx genes play an important role in eye, tooth, pituitary and umbilical region development as evidenced by Rieger syndrome and iris hypoplasia phenotypes, resulting from mutations in the RIEG1 gene and by expression studies [4].
• In order to characterize further the Pitx gene family we searched mouse cDNA libraries to identify additional members [4].

Anatomical context of Pitx1

• Pitx1 expression is detected in early development in a widespread pattern, in both epithelium and mesenchyme, covering the tooth-forming region in the mandible, and is then maintained in the dental epithelium from the bud stage to the late bell stage [5].
• Ptx1 is expressed in most pituitary-derived cell lines and as is the related Ptx2 (Rieger) gene [6].
• Comparative sequencing studies in complete and pelvic-reduced Pungitius revealed no differences in the Pitx1 coding sequences, but Pitx1 expression was absent from the prospective pelvic region of larvae from pelvic-reduced parents [7].
• Although Pitx1 is expressed throughout developing hindlimb buds, Pitx2 is not expressed in limb bud mesenchyme itself, but is co-expressed with Pitx1 in the presumptive hindlimb field before bud growth [8].
• In the adult pituitary gland, Ptx1 appears to be recruited for cell-specific transcription of the POMC gene [9].

Physical interactions of Pitx1

• We show that Pitx proteins interact via their conserved homeodomain with the DNA-binding domain of GCMa [10].
• Pitx-1 interacted directly with c-Jun, and the HD was sufficient for this interaction [11].

Regulatory relationships of Pitx1

• Bead implantation experiments demonstrate that ectopic expression of Fgf8 can induce/maintain the expression of both Pitx1 and Pitx2 at E9 [5].
• Mesenchymal patterning by Hoxa2 requires blocking Fgf-dependent activation of Ptx1 [12].
• Furthermore, Pitx proteins influence GCMa-dependent promoter activation in a cell-specific manner [10].

Other interactions of Pitx1

• Thus, these experiments place Ptx1 upstream of Lim3/Lhx3 in a cascade of regulators that appear to work in a combinatorial code to direct pituitary-, lineage-, and promoter-specific transcription [6].
• In this study, we examined the expression and regulation of Pitx1 and Pitx2 during mouse tooth development [5].
• Our results support a role for Tbx5 and Tbx4, but not for Pitx1, in initiation of limb outgrowth [13].
• Hoxa2 interferes with the Ptx1 activating process, which is dependent on Fgf signals from the epithelium [12].
• As a consequence, Pitx proteins and GCMa exhibit cooperative DNA binding [10].

Analytical, diagnostic and therapeutic context of Pitx1

• Sequence analysis of the 5'-flanking region revealed a number of putative regulatory elements including Sp1, Egr-1 and Pitx binding sites [14].

References