ALK3

BMPR1A (bone morphogenetic protein receptor type 1A) is also known as ALK3. Though some functions of ALK3 suggest similarity to ALK2, this protein has substantial sequence similarity with a different ALK family member, ALK6. Currently, it is known that many BMPs (BMP2, 4, 5, 6, 7, 8, 14, 15), GDF6, GDF7, and AMH can bind to ALK3 with some affinity to initiate differential downstream action. Global knockout of ALK3 is embryonic lethal. ALK3 is expressed in cells of the osteo lineage and bone marrow and is necessary for post-natal bone formation; as such, it is suggested that the main function of ALK3 is osteogenesis. Mice with conditional knockout of ALK3 in cartilage lack growth of the long bones, however this tissue gets replaced with bone-like tissue, supporting a role of ALK3 in cell fate and osteogenesis. Conditional deletion of Alk3 from osteoblasts produces a similar phenotype. These mice have increased bone formation in the trabecular bone, vertebrae, tail, and ribs, coupled with a reduction in osteoclastogenesis. Unlike ALK2, ALK3 has additional critical roles in development. Deletion of ALK3 in Xenopus results in dorsalized embryos and defects in the eye. Myocardial- and neural crest-specific knockouts of ALK3 show drastic developmental defects. Epicardial-specific deletion of ALK3 in mice results in atypical developmental of the atrioventricular sulcus and annulus fibrosis within the cardia. Additionally, when ALK3 is deleted early (at weaning or early adulthood) from the foregut, mice have improper gastric patterning, as well as a reduced number of parietal cells and increased number of endocrine cells.