Bmpr1a, the type IA bone morphogenetic protein receptor, is essential for BMP signaling [2]. It is involved in multiple biological processes such as cartilage development, endochondral ossification, and cell differentiation. The BMP signaling pathway, in which Bmpr1a is a key component, plays a crucial role in various biological functions and disease processes [2]. Genetic mouse models have been valuable in studying Bmpr1a.

In adult mice, deletion of endothelial Bmpr1a (Bmpr1aiECKO) leads to excessive endothelial-mesenchymal transition (EndoMT), resulting in PAH-like symptoms. Lineage tracing shows an increase in endothelial-derived smooth muscle cells. Mechanistically, BMPR1A activation promotes ID2-ZEB1 interaction, which attenuates Tgfbr2 transcription, preventing excessive EndoMT [1]. In Col2+ cells, conditional knockout of fibroblast growth factor receptor 3 (FGFR3) promotes acquired heterotopic ossification (HO) development. FGFR3 deficiency in Prox1+ lymphatic endothelial cells (LECs) exacerbates HO through decreased local lymphatic formation in a Bmpr1a-pSmad1/5-dependent manner [3]. Deletion of mesenchymal Bmpr1a in mice disrupts normal lung branching morphogenesis, causing congenital pulmonary cysts. This is associated with severe deficiency of airway smooth muscle cells and subepithelial elastin fibers, as well as ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis [4].

In conclusion, Bmpr1a is vital for maintaining endothelial identity, preventing excessive EndoMT, and is involved in cartilage development, endochondral ossification, and lymphatic regulation, as well as lung development. Mouse models with Bmpr1a knockout or conditional knockout have significantly contributed to understanding its role in diseases such as pulmonary arterial hypertension, heterotopic ossification, and congenital pulmonary cysts.