Department of Craniofacial Development, Dental Institute, King's College London, London, United Kingdom.
Dev Dyn. 2010 Oct;239(10):2674-84. doi: 10.1002/dvdy.22406.
Hypohidrotic ectodermal dysplasia (HED) is characterized by defective ectodermal organ development. This includes the salivary glands (SGs), which have an important role in lubricating the oral cavity. In humans and mice, HED is caused by mutations in Ectodysplasin A (Eda) pathway genes. Various phenotypes of the mutant mouse Eda(Ta/Ta), which lacks the ligand Eda, can be rescued by maternal injection or in vitro culture supplementation with recombinant EDA. However, the response of the SGs to this treatment has not been investigated. Here, we show that the submandibular glands (SMGs) of Eda(Ta/Ta) mice exhibit impaired branching morphogenesis, and that supplementation of Eda(Ta/Ta) SMG explants with recombinant EDA rescues the defect. Supplementation of Edar(dlJ/dlJ) SMGs with recombinant Sonic hedgehog (Shh) also rescues the defect, whereas treatment with recombinant Fgf8 does not. This work is the first to test the ability of putative Eda target molecules to rescue Eda pathway mutant SMGs.
先天性外胚层发育不全（HED）的特征是外胚层器官发育缺陷。这包括唾液腺（SGs），它们在口腔润滑中起着重要作用。在人类和小鼠中，HED 是由 Ectodysplasin A（Eda）途径基因突变引起的。缺乏配体 Eda 的突变型小鼠 Eda（Ta/Ta）的各种表型可以通过母体注射或体外培养补充重组 EDA 来挽救。然而，尚未研究 SG 对这种治疗的反应。在这里，我们表明 Eda（Ta/Ta）小鼠的颌下腺（SMG）表现出分支形态发生受损，并且用重组 EDA 补充 Eda（Ta/Ta）SMG 外植体可挽救该缺陷。用重组 Sonic hedgehog（Shh）补充 Edar（dlJ/dlJ）SMG 也可挽救该缺陷，而用重组 Fgf8 处理则不能。这项工作首次测试了假定的 Eda 靶分子拯救 Eda 途径突变型 SMG 的能力。
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