Involvement of a novel Tnf receptor homologue in hair follicle induction
Involvement of a novel Tnf receptor homologue in hair follicle induction
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DOI：
10.1038/11943
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发表时间：
1999-08-01
期刊：
影响因子：
30.8
通讯作者：
Overbeek, PA
中科院分区：
文献类型：
--
作者：
Headon, DJ;Overbeek, PA
尽管已知诱导性相互作用对于许多脊椎动物组织中细胞命运的特化至关重要，但负责传递这种信息的信号和受体在很大程度上仍未被确定。无毛（dl）基因突变的小鼠在毛囊诱导方面存在缺陷，缺乏汗腺且牙齿畸形（1）。这些结构起源于外胚层基板，它们内陷到下方的间充质中并分化形成特定的器官（2 - 4）。dl基因的定位克隆始于对转基因家族OVE1的鉴定。该家族的一个分支，dl(OVE1B)，由于转基因整合在dl位点处有一个约600kb的缺失。突变位点已在该家族中进行了物理定位（5），并且一个200kb的小鼠YAC克隆，YAC D9，已被鉴定出来，并显示能挽救自发的dl(Jackson)（dl(J)，隐性）和Dl(sleek)（Dl(slk)，显性负性）突变体中的dl表型（6）。在此我们报道dl基因的定位克隆，它编码肿瘤坏死因子（Tnf）受体（Tnfr）家族的一个新成员。突变表型和dl表达模式表明该基因编码一种决定毛囊命运的受体。它的配体可能是斑猫（Ta）基因的产物，因为Ta突变体具有与dl（参考文献1）突变体相同的表型，并且Ta编码一种类似Tnf的蛋白质。
Although inductive interactions are known to be essential for specification of cell fate in many vertebrate tissues, the signals and receptors responsible for transmitting this information remain largely unidentified. Mice with mutations in the downless (dl) gene have defects in hair follicle induction, lack sweat glands and have malformed teeth(1). These structures originate as ectodermal placodes, which invaginate into the underlying mesenchyme and differentiate to form specific organs(2-4). Positional cloning of the dl gene began with identification of the transgenic family OVE1. One branch of the family, dl(OVE1B), Carries an approximately 600-kb deletion at the dl locus caused by transgene integration. The mutated locus has been physically mapped in this family(5), and a 200-kb mouse YAC clone, YAC D9, has been identified and shown to rescue the dl phenotype in the spontaneous dl(Jackson) (dl(J), recessive) and Dl(sleek) (Dl(slk), dominant negative) mutants(6), Here we report the positional cloning of the dl gene, which encodes a novel member of the tumour necrosis factor (Tnf) receptor (Tnfr) family. The mutant phenotype and dl expression pattern suggests that this gene encodes a receptor that specifies hair follicle fate. Its ligand is likely to be the product of the tabby (Ta) gene, as Ta mutants have a phenotype identical to that of dl (ref. 1) mutants and Ta encodes a Tnf-like protein.