Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, Ghent, Belgium; Molecular Signaling and Cell Death Unit, Inflammation Research Center, Ghent University, Ghent, Belgium.
Developmental Biology Program, Institute of Biotechnology, University of Helsinki, P.O.B. 56, 00014 Helsinki, Finland.
Semin Immunol. 2014 Jun;26(3):220-8. doi: 10.1016/j.smim.2014.05.002. Epub 2014 Jun 10.
Ectodysplasin (Eda) is the most studied tumor necrosis ligand in the field of developmental biology. In all vertebrates studied so far, inactivating germline mutations in Eda lead to the genetic disease called hypohidrotic ectodermal dysplasia (HED). In humans, HED is a life-threatening condition in particular in infants due to absent or severely reduced sweating leading to hyperthermia. HED is also characterized by sparse hair, and oligo- or anodontia. Research of the Eda pathway has not only increased our knowledge on ectodermal appendage development and etiology of developmental disorders, but also on evolution of several vertebrate species including humankind. Studies on mouse and dog models of HED has led to one of the most stunning breakthroughs in applied developmental biology research by showing that a short-term treatment of neonates with a synthetic ligand corrects many of the HED-associated traits. Eighteen years after the identification of EDA as the causative gene in HED, a phase II trial aiming at permanent correction of the disease is now ongoing. This review summarizes the latest discoveries in the Eda field and points to areas that need further investigation such as the possible involvement of Eda in cell migration, stem cell maintenance, or cancer.
外胚层发育不全素（Eda）是发育生物学领域研究最多的肿瘤坏死配体。在迄今为止研究的所有脊椎动物中，Eda 的种系失活突变导致一种称为少汗性外胚层发育不良（HED）的遗传疾病。在人类中，HED 是一种危及生命的疾病，特别是在婴儿中，由于缺乏或严重减少出汗导致体温过高。HED 还表现为稀疏的毛发和少牙或无牙。对 Eda 途径的研究不仅增加了我们对表皮附属物发育和发育障碍病因的认识，而且还增加了对包括人类在内的几个脊椎动物物种的进化的认识。对 HED 小鼠和犬模型的研究取得了最引人注目的应用发育生物学研究突破之一，表明对新生儿进行短期合成配体治疗可纠正许多 HED 相关特征。在确定 EDA 为 HED 的致病基因 18 年后，目前正在进行旨在永久纠正该疾病的 II 期试验。这篇综述总结了 Eda 领域的最新发现，并指出了需要进一步研究的领域，如 Eda 在外胚层细胞迁移、干细胞维持或癌症中的可能参与。
