Hair cycle regulation of Hedgehog signal reception
Hair cycle regulation of Hedgehog signal reception
复制标题
DOI：
10.1016/s0012-1606(02)00042-8
复制
发表时间：
2003-03-15
影响因子：
2.7
通讯作者：
Higgins, K
中科院分区：
文献类型：
--
作者：
Oro, AE;Higgins, K
像毛囊这样的自我更新器官的正确模式，需要对生长信号进行精确的调节。皮肤中的Sonic Hedgehog(Shh)信号部分通过调节Gli转录因子调控毛囊上皮的生长和形态发生。虽然Shh靶基因的异位诱导会导致毛囊肿瘤，如基底细胞癌，但Shh信号在毛发发育的周期过程中如何正常发挥作用尚不清楚。在这里，我们表明，在毛发周期中，Shh的表达和皮肤细胞对Shh信号的反应能力在空间和时间上都受到调节。Shh靶基因的诱导通常只发生在生长期毛囊中，以响应Shh的表达。然而，在Patched1杂合子小鼠中，假定的肿瘤前体仅在生长期毛囊和毛囊间角质形成细胞中伴随着Shh靶基因转录的诱导。异位生产的Gli1积累了Gli蛋白，并在生长期诱导Shh靶基因和上皮性肿瘤，而不是在其他阶段，这表明在Gli蛋白积累的水平上存在有限的竞争能力。多能细胞之间生长信号的传递和接收在时间和空间上受到限制，以促进循环模式的形成。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
Proper patterning of self-renewing organs, like the hair follicle, requires exquisite regulation of growth signals. Sonic hedgehog (Shh) signaling in skin controls the growth and morphogenesis of hair follicle epithelium in part through regulating the Gli transcription factors. While ectopic induction of Shh target genes leads to hair follicle tumors, such as basal cell carcinomas, how Shh signaling normally functions during the cyclic process of hair development is unknown. Here, we show that, during the hair cycle, Shh expression and the ability of skin cells to respond to Shh signaling is spatially and temporally regulated. Induction of Shh target genes normally occurs only in the anagen hair follicle in response to expression of Shh. However, in patched1 heterozygous mice, putative tumor precursors form with concomitant induction of Shh target gene transcription only during anagen in follicular and interfollicular keratinocytes. Ectopic production of Gli1 accumulates Gli protein and induces Shh target genes and epithelial tumors at anagen but not other stages, pointing to a restricted competence occurring at the level of Gli protein accumulation. Delivery and reception of growth signals among multipotent cells are restricted in time and space to facilitate cyclic pattern formation. (C) 2003 Elsevier Science (USA). All rights reserved.