Department of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Bioengineering, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
Nat Commun. 2024 Nov 12;15(1):9806. doi: 10.1038/s41467-024-53642-2.
Bone Morphogenetic Protein (BMP) signaling is essential for craniofacial development, though little is known about the mechanisms that govern BMP secretion. We show that depolarization induces calcium-dependent BMP4 release from mouse embryonic palate mesenchyme. We show endogenous transient changes in intracellular calcium occur in cranial neural crest cells, the cells from which embryonic palate mesenchyme derives. Waves of transient changes in intracellular calcium suggest that these cells are electrically coupled and may temporally coordinate BMP release. These transient changes in intracellular calcium persist in palate mesenchyme cells from embryonic day 9.5 to 13.5 mice. Disruption of a potassium channel called Kcnj2 significantly decreases the amplitude of calcium transients and the ability of cells to secrete BMP. Kcnj2 knockout mice have cleft palate and reduced BMP signaling. Our data suggest that temporal control of developmental cues is regulated by ion channels, depolarization, and intracellular calcium for mammalian craniofacial morphogenesis.
骨形态发生蛋白 (BMP) 信号对于颅面发育是必不可少的，但对于控制 BMP 分泌的机制知之甚少。我们发现去极化诱导来自小鼠胚胎腭间充质的钙依赖性 BMP4 释放。我们发现颅神经嵴细胞中存在内源性瞬时变化的细胞内钙，而胚胎腭间充质来源于这些细胞。细胞内钙的瞬时变化波表明这些细胞是电偶联的，并且可能在时间上协调 BMP 的释放。来自胚胎第 9.5 天至 13.5 天的小鼠的腭间充质细胞中存在这些瞬时的细胞内钙变化。一种称为 Kcnj2 的钾通道的破坏显着降低钙瞬变的幅度和细胞分泌 BMP 的能力。Kcnj2 基因敲除小鼠具有腭裂和 BMP 信号减少。我们的数据表明，离子通道、去极化和细胞内钙通过调节 temporally 控制发育线索，从而调节哺乳动物颅面形态发生。
