Vauclair Sophie, Nicolas Michael, Barrandon Yann, Radtke Freddy
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland.
Dev Biol. 2005 Aug 1;284(1):184-93. doi: 10.1016/j.ydbio.2005.05.018.
Notch genes encode evolutionarily conserved large, single transmembrane receptors, which regulate many cell fate decisions and differentiation processes during fetal and postnatal life. Multiple Notch receptors and ligands are expressed in both developing and adult epidermis and hair follicles. Proliferation and differentiation of these two ectodermal-derived structures have been proposed to be controlled in part by the Notch pathway. Whether Notch signaling is involved in postnatal hair homeostasis is currently unknown. Here, we investigate and compare the role of the Notch1 receptor during embryonic hair follicle development and postnatal hair homeostasis using Cre-loxP based tissue specific and inducible loss-of-function approaches. During embryonic development, tissue-specific ablation of Notch1 does not perturb formation and patterning of hair follicle placodes. However, Notch1 deficient hair follicles invaginate prematurely into the dermis. Embryonic as well as postnatal inactivation of Notch1 shortly after birth or in adult mice results in almost complete hair loss followed by cyst formation. The first hair cycle of Notch1 deficient mice is characterized by shortened anagen and a premature entry into catagen. These data show that Notch1 is essential for late stages of hair follicle development during embryogenesis as well as for post-natal hair follicle development and hair homeostasis.
Notch基因编码进化上保守的大型单跨膜受体，其在胎儿期和出生后调节许多细胞命运决定和分化过程。多种Notch受体和配体在发育中的和成年的表皮及毛囊中表达。这两种外胚层来源结构的增殖和分化被认为部分受Notch信号通路控制。目前尚不清楚Notch信号是否参与出生后毛发的稳态维持。在这里，我们使用基于Cre-loxP的组织特异性和诱导性功能丧失方法，研究并比较了Notch1受体在胚胎毛囊发育和出生后毛发稳态维持中的作用。在胚胎发育过程中，Notch1的组织特异性缺失不会干扰毛囊基板的形成和模式。然而，Notch1缺陷的毛囊会过早地侵入真皮。在出生后不久或成年小鼠中Notch1的胚胎期及出生后失活会导致几乎完全脱发，随后形成囊肿。Notch1缺陷小鼠的第一个毛发周期的特征是生长期缩短和过早进入退行期。这些数据表明，Notch1对于胚胎发育过程中毛囊发育的后期阶段以及出生后毛囊发育和毛发稳态维持至关重要。
