Notch1 is essential for postnatal hair follicle development and homeostasis

Abstract

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.

Expression of Notch pathway genes in mammalian epidermis and modulation by β‐Catenin

“…The increase in gene transcripts during anagen is consistent with the observation that Notch activity is necessary for the growth phase of the hair cycle (Pan et al, 2004;Vauclair et al, 2005;Estrach et al, 2006). It is interesting that Hes1, Hes5, and HeyL are expressed in the precortex of the hair follicle bulb, because this is a site of nuclear ␤-catenin and Lef1 expression and is also where lineage commitment occurs (DasGupta and Fuchs, 1999;Niemann and Watt, 2002).…”

“…Conversely, activation of the Wnt effector, ␤-catenin, is sufficient to induce ectopic hair follicles in adult epidermis . Notch activation is not required for hair follicle formation in the embryo, but blocking Notch signalling in postnatal epidermis results in conversion of hair follicles into interfollicular epidermal cysts (Yamamoto et al, 2003;Pan et al, 2004;Vauclair et al, 2005;Estrach et al, 2006). In contrast to ␤-catenin activation, activation of Notch is not sufficient to induce anagen or ectopic hair follicle formation.…”

CROSSTALK BETWEEN Nrf2 AND NOTCH SIGNALING

“…This crosstalk can probably influence the adaptive defenses of the stem cells and be important for the maintenance of homeostasis of the niche. In addition to hepato-cholagionenesis in adult liver [47,84,85], the airways basal stem cell system for proliferating or self-renewal in the lung [43], enterogenesis in the intestinal crypt [86], adult neurogenesis occurring in the subventricular zone and/or the dentate gyrus of the hippocampus in the central nervous system [15,87,88], dermatogenesis in the skin [17,89,90], osteogenesis in bone [91,92], cell fate determination in hematopoiesis [93,94] and angiogenesis in various tissues [95] might all be valuable settings for further evaluation ( Figure 5A). …”

Biology of Human Hair: Know Your Hair to Control It

“…In the absence of Notch signaling, the hair shaft still forms and contains appropriately positioned cells expressing markers for each fate; however, because IRS cells fail to adhere to each other, the follicular architecture cannot be sustained, which leads to the transformation of these aberrant HF into epidermal cysts [92][93][94][95]. Very recently, Demehri and Kopan [96] proposed that Notch acting on bi-potential bulge stem cells, or their uncommitted migratory descendents, plays an inhibitory role in preventing bulge stem cells from differentiating into epidermal cells, thus ensuring the follicular fate.…”