St-Jacques B, Dassule H R, Karavanova I, Botchkarev V A, Li J, Danielian P S, McMahon J A, Lewis P M, Paus R, McMahon A P
Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Curr Biol. 1998 Sep 24;8(19):1058-68. doi: 10.1016/s0960-9822(98)70443-9.
The skin is responsible for forming a variety of epidermal structures that differ amongst vertebrates. In each case the specific structure (for example scale, feather or hair) arises from an epidermal placode as a result of epithelial-mesenchymal interactions with the underlying dermal mesenchyme. Expression of members of the Wnt, Hedgehog and bone morphogenetic protein families (Wnt10b, Sonic hedgehog (Shh) and Bmp2/Bmp4, respectively) in the epidermis correlates with the initiation of hair follicle formation. Further, their expression continues into either the epidermally derived hair matrix which forms the hair itself, or the dermal papilla which is responsible for induction of the hair matrix. To address the role of Shh in the hair follicle, we have examined Shh null mutant mice.
We found that follicle development in the Shh mutant embryo arrested after the initial epidermal-dermal interactions that lead to the formation of a dermal papilla anlage and ingrowth of the epidermis. Wnt10b, Bmp2 and Bmp4 continued to be expressed at this time, however. When grafted to nude mice (which lack T cells), Shh mutant skin gave rise to large abnormal follicles containing a small dermal papilla. Although these follicles showed high rates of proliferation and some differentiation of hair matrix cells into hair-shaft-like material, no hair was formed.
Shh signaling is not required for initiating hair follicle development. Shh signaling is essential, however, for controlling ingrowth and morphogenesis of the hair follicle.
皮肤负责形成各种在脊椎动物中各不相同的表皮结构。在每种情况下，特定结构（例如鳞片、羽毛或毛发）由表皮基板产生，这是上皮与下方真皮间充质相互作用的结果。表皮中Wnt、Hedgehog和骨形态发生蛋白家族成员（分别为Wnt10b、音猬因子（Shh）和Bmp2/Bmp4）的表达与毛囊形成的起始相关。此外，它们的表达持续到形成毛发本身的表皮来源的毛基质，或负责诱导毛基质的真皮乳头中。为了研究Shh在毛囊中的作用，我们检查了Shh基因敲除突变小鼠。
我们发现，Shh突变胚胎中的毛囊发育在导致真皮乳头原基形成和表皮向内生长的初始表皮 - 真皮相互作用之后停滞。然而，此时Wnt10b、Bmp2和Bmp4仍继续表达。当移植到裸鼠（缺乏T细胞）时，Shh突变皮肤产生了含有小真皮乳头的大的异常毛囊。尽管这些毛囊显示出高增殖率，并且一些毛基质细胞分化为毛干样物质，但未形成毛发。
Shh信号传导对于启动毛囊发育不是必需的。然而，Shh信号传导对于控制毛囊的向内生长和形态发生至关重要。
