Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis.

Abstract

Bone morphogenetic proteins (BMPs) are secreted proteins that interact with cell-surface receptors and are believed to play a variety of important roles during vertebrate embryogenesis. Bmpr, also known as ALK-3 and Brk-1, encodes a type I transforming growth factor-~ (TGF-[3) family receptor for BMP-2 and BMP-4. Bmpr is expressed ubiquitously during early mouse embryogenesis and in most adult mouse tissues. To study the function of Bmpr during mammalian development, we generated Bmpr-mutant mice. After embryonic day 9.5 (E9.5), no homozygous mutants were recovered from heterozygote matings. Homozygous mutants with morphological defects were first detected at E7.0 and were smaller than normal. Morphological and molecular examination demonstrated that no mesoderm had formed in the mutant embryos. The growth characteristics of homozygous mutant blastocysts cultured in vitro were indistinguishable from those of controls; however, embryonic ectoderm (epiblast) cell proliferation was reduced in all homozygous mutants at E6.5 before morphological abnormalities had become prominent. Teratomas arising from E7.0 mutant embryos contained derivatives from all three germ layers but were smaller and gave rise to fewer mesodermal cell types, such as muscle and cartilage, than controls. These results suggest that signaling through this type I BMP-2/4 receptor is not necessary for preimplantation or for initial postimplantation development but may be essential for the inductive events that lead to the formation of mesoderm during gastrulation and later for the differentiation of a subset of mesodermal cell types.

Conditional knockout of the Smad1 gene

“…Smad1 is expressed in a variety of adult mouse tissues and cells (Huang et al, 2000;Flanders et al, 2001;Brorson et al, 2001) and is thought to mediate signals primarily from the bone morphogenetic proteins (BMPs), although it can also transduce signals from TGF-␤ and Müllerian Inhibiting Substance (Liu et al, 1998;Oh et al, 2000;Clarke et al, 2001). Consistent with the critical roles of the BMPs in early embryonic patterning and morphogenesis (Mishina et al, 1995;Ahn et al, 2001), targeted deletion of the Smad1 gene results in early embryonic lethality due to failure of the allantois to fuse to the chorion (Lechleider et al, 2002;Tremblay et al, 2001). To address its function in the adult, we have generated a Smad1 conditional knockout mouse using the Cre-loxP system.…”

The BMP signaling and in vivo bone formation

“…Homozygous mutants with morphological defects are first detected at E7.5. No mesoderm forms in the mutant embryos, suggesting that Bmpr1a is essential for the inductive events that lead to the formation of mesoderm during gastrulation (Mishina et al, 1995). Using CreloxP CKO approach, the Bmpr1a gene has been deleted in different tissues to investigate its specific functions.…”

Co-ordinating Notch, BMP, and TGF-β signaling during heart valve development

“…Targeted loss of the BMP receptors, ALK2, ALK3, and BMPRII, result in embryonic lethality at gastrulation [57][58][59], and thus the role of BMP receptors in heart development was examined using tissue-specific deletion. Endocardial cells lacking ALK2 fail to transform into mesenchymal cells and populate the cardiac cushions and embryos that do survive to E14.5 have ventricular septal defects and valve abnormalities [45].…”