Disease relevance of Bmpr1a

• By contrast, Bmpr1a mutant mice displayed decreased apoptosis and augmented Fgf8 expression in the DUE associated with GT hyperplasia [1].
• In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption [2].
• Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome [3].
• Disruption of a Bmp type I receptor gene, Bmpr1a, leads to no detectable eye abnormality [4].
• Three days after the femoral fracture, expression of BMPR-IA and -IB was up-regulated in cells at the proliferating osteogenic layer of the periosteum [5].

High impact information on Bmpr1a

• These results identify Bmpr1a as a type I receptor for Amh-induced regression of Müllerian ducts [6].
• Because Bmpr1a is evolutionarily conserved, these findings indicate that a component of the BMP signaling pathway has been co-opted during evolution for male sexual development in amniotes [6].
• Requirement of Bmpr1a for Müllerian duct regression during male sexual development [6].
• In this study, we show that a targeted null mutation of Ecsit, encoding a signaling intermediate of the Toll pathway, leads to reduced cell proliferation, altered epiblast patterning, impairment of mesoderm formation, and embryonic lethality at embryonic day 7.5 (E7.5), phenotypes that mimic the Bmp receptor type1a (Bmpr1a) null mutant [7].
• By generation of compound mutants, we also show that beta-catenin acts downstream of the BMP receptor IA in AER induction, but upstream or parallel in dorsal-ventral patterning [8].

Biological context of Bmpr1a

• To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice [2].
• Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo [9].
• These results provide definitive genetic evidence that epithelial Bmpr1a is required for completion of tooth morphogenesis, and regulates terminal differentiation and proliferation in postnatal hair follicles [10].
• Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects [11].
• In contrast, absence of BMPR-IA did not significantly diminish ADAS osteogenesis [12].

Anatomical context of Bmpr1a

• To further define the requirement for BMP signaling in the differentiation of blood, endothelial and smooth muscle cells from FLK1(+) mesoderm, we inactivated Alk3 (Bmpr1a) in FLK1(+) cells by crossing Alk3(floxed/floxed) and Flk1(+/Cre)Alk3(+/floxed) mice [13].
• We have ablated Bmpr1a specifically in the neural crest, beginning at the five-somite stage [14].
• Mouse embryos lacking Bmpr1a fail to gastrulate, complicating studies on the requirements for BMP signaling in germ layer development [15].
• The Type I Bone morphogenetic protein receptor gene (Bmpr/Tfr-11/Brk-1) is expressed at low levels in the epithelium and in the distal mesenchyme [16].
• We generated a conditional knockout of the gene encoding BMPR-IA (Bmpr) that disrupted BMP signaling in the limb ectoderm [17].

Associations of Bmpr1a with chemical compounds

• Biotin surface-labeling experiments revealed that the 85 kDa ALK-3 protein was constitutively associated with a novel 140 kDa surface glycoprotein [18].
• Importantly, inhibition of the p38 MAPK pathway by SB203580 overcomes the block in deriving ES cells from blastocysts lacking a functional Alk3, the BMP type IA receptor [19].
• However, a soluble form of BMP receptor IA inhibited the induction of ALPase activity by ascorbic acid [20].

Physical interactions of Bmpr1a

• Here, we demonstrate by biosensor analysis that GDF-5 also binds to BMP receptor IA (BMPR-IA) but with approximately 12-fold lower affinity [21].

Regulatory relationships of Bmpr1a

• Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated beta-catenin [22].

Other interactions of Bmpr1a

• In the present study, we examine the effect of BMP4 on the development of metanephric and periureteral mesenchymal cells, which express the BMP type I receptor gene, Bmpr1a (Alk3) [23].
• Immunolabeling of pituitary sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope cells [24].
• By contrast, ALK-2 and ALK-3 immunostainings in E14 were barely detectable [25].
• ALK-3 and ALK-5 mRNAs first decreased on day 14 and increased again on day 21 [26].
• Whereas mice deficient in type 1 receptors Bmpr1a or Bmpr1b in cartilage are able to form intact cartilaginous elements, double mutants develop a severe generalized chondrodysplasia [9].

Analytical, diagnostic and therapeutic context of Bmpr1a

• The distribution of ALK-3 and ALK-6 mRNA in the postimplantation mouse embryo [6.5-15.5 days postcoitum (pc)] was studied by in situ hybridization [27].
• On Western blot analyses, we found that the native 85 kDa native ALK-3 protein was expressed in a number of murine tissues; protein and mRNA levels did not necessarily correlate [18].
• Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft [22].
• In the present study, we examined the involvement of functional BMP-2 type I receptors in signal transduction in C2C12 cells, which expressed mRNA for BMPR-IA, but not for BMPR-IB in Northern blotting [28].
• Expression of ALK3 was also examined by immunofluorescence and immunoblotting [29].

References