Proper development of taste organs including the tongue and taste papillae requires interactions with the underlying mesenchyme through multiple molecular signaling pathways. The effects of bone morphogenetic proteins (BMPs) and antagonists are profound, however, the tissue‐specific roles of distinct receptors are largely unknown. Here, we report that constitutive activation (ca) of ALK2‐BMP signaling in the tongue mesenchyme (marked by Wnt1‐Cre) caused microglossia—a dramatically smaller and misshapen tongue with a progressively severe reduction in size along the anteroposterior axis and absence of a pharyngeal region. At E10.5, the tongue primordia (branchial arches 1–4) formed in Wnt1‐Cre/caAlk2 mutants while each branchial arch responded to elevated BMP signaling distinctly in gene expression of BMP targets (Id1, Snai1, Snai2, and Runx2), proliferation (Cyclin‐D1) and apoptosis (p53). Moreover, elevated ALK2‐BMP signaling in the mesenchyme resulted in apparent defects of lingual epithelium, muscles, and nerves. In Wnt1‐Cre/caAlk2 mutants, a circumvallate papilla was missing and further development of formed fungiform papillae was arrested in late embryos. Our data collectively demonstrate that ALK2‐BMP signaling in the mesenchyme plays essential roles in orchestrating various tissues for proper development of the tongue and its appendages in a region‐specific manner.

中文翻译：

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间充质 ALK2-BMP 信号传导活性增加会导致小舌后部截短和舌组织紊乱。


包括舌头和味觉乳头在内的味觉器官的正常发育需要通过多种分子信号传导途径与底层间充质相互作用。骨形态发生蛋白（BMP）和拮抗剂的作用是深远的，然而，不同受体的组织特异性作用在很大程度上尚不清楚。在这里，我们报告舌间充质中 ALK2-BMP 信号的组成性激活 (ca)（由Wnt1-Cre标记）导致小舌症——一种显着较小且畸形的舌头，沿着前后轴尺寸逐渐严重减小，并且缺乏舌咽部区域。在 E10.5，舌原基（鳃弓 1-4）在Wnt1-Cre/caAlk2突变体中形成，而每个鳃弓在 BMP 靶标（ Id1 、 Snai1 、 Snai2和Runx2 ）的基因表达中对升高的 BMP 信号做出明显的反应，增殖（ Cyclin-D1 ）和凋亡（ p53 ）。此外，间充质中 ALK2-BMP 信号传导的升高导致舌上皮、肌肉和神经的明显缺陷。在Wnt1-Cre/caAlk2突变体中，圆形乳头缺失，并且形成的菌状乳头的进一步发育在晚期胚胎中被阻止。我们的数据共同表明，间充质中的 ALK2-BMP 信号在协调各种组织以区域特异性方式正常发育舌头及其附属物方面发挥着重要作用。