A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning
A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning
复制标题
DOI：
10.1242/dev.00788
复制
发表时间：
2003-11-01
期刊：
影响因子：
4.6
通讯作者：
Dickson, C
中科院分区：
文献类型：
--
作者：
Petiot, A;Conti, FJA;Dickson, C
为了了解Fgf信号在皮肤和毛囊发育中的作用，我们分析了Fgfr 2-IIIb及其主要配体Fgf 10缺陷小鼠的表型。这些研究表明，在Fgfr 2-IIIb缺失的小鼠中发现的严重表皮发育不全是由缺乏通常导致分层表皮的基底细胞增殖引起的。尽管在足月时，Fgfr 2-IIIb缺失小鼠的表皮只有两到三个细胞厚，但它表达表皮分化的经典标志物并建立功能屏障。缺乏Fgf 10的小鼠表现出类似但不太严重的表皮发育不全。相比之下，Fgfr 2-IIIb（-/-），而不是Fgf 10（-/-），小鼠产生的毛囊显着减少，他们的毛囊发育迟缓。移植到裸鼠后，Fgfr 2-IIIb（-/-）皮肤移植物显示毛发形成受损，毛发密度降低，并产生异常皮毛。Lef 1、Shh和Bmp 4在Fgfr 2-IIIb（-/-）小鼠发育中的毛囊中的表达与野生型相似。这些结果表明，FGF信号正向调节形成正常复层表皮和启动毛基板形成所需的角质形成细胞的数量。此外，Fgf信号是毛皮毛发生长和图案化所必需的。
To understand the role Fgf signalling in skin and hair follicle development, we analysed the phenotype of mice deficient for Fgfr2-IIIb and its main ligand Fgf10. These studies showed that the severe epidermal hypoplasia found in mice null for Fgfr2-IIIb is caused by a lack of the basal cell proliferation that normally results in a stratified epidermis. Although at term the epidermis of Fgfr2-IIIb null mice is only two to three cells thick, it expresses the classical markers of epidermal differentiation and establishes a functional barrier. Mice deficient for Fgf10 display a similar but less severe epidermal hypoplasia. By contrast, Fgfr2-IIIb(-/-), but not Fgf10(-/-), mice produced significantly fewer hair follicles, and their follicles were developmentally retarded. Following transplantation onto nude mice, grafts of Fgfr2-IIIb(-/-) skin showed impaired hair formation, with a decrease in hair density and the production of abnormal pelage hairs. Expression of Lef1, Shh and Bmp4 in the developing hair follicles of Fgfr2-IIIb(-/-) mice was similar to wild type. These results suggest that Fgf signalling positively regulates the number of keratinocytes needed to form a normal stratified epidermis and to initiate hair placode formation. In addition, Fgf signals are required for the growth and patterning of pelage hairs.