First Author | Turkoz M | Year | 2016 |
Journal | J Invest Dermatol | Volume | 136 |
Issue | 6 | Pages | 1106-15 |
PubMed ID | 26940862 | Mgi Jnum | J:235539 |
Mgi Id | MGI:5796729 | Doi | 10.1016/j.jid.2016.02.018 |
Citation | Turkoz M, et al. (2016) The Notch Intracellular Domain Has an RBPj-Independent Role during Mouse Hair Follicular Development. J Invest Dermatol 136(6):1106-15 |
abstractText | Ligand-dependent activation, gamma-secretase-processed cleavage, and recombining binding protein Jk (RBPj)-mediated downstream transcriptional activities of Notch receptors constitute the "canonical" Notch signaling pathway, which is essential for skin organogenesis. However, in Msx2-Cre mice, keratinocyte-specific deletion of the Rbpj gene in utero produced a significantly milder phenotype than either global Notch or gamma-secretase loss. Herein, we investigated the underlying mechanisms for this apparent noncanonical signal using mouse genetics. We found no evidence that ligand back-signaling contributed to skin organogenesis. The perdurance of RBPj protein did not establish an epigenetic memory of a canonical signal in the youngest epidermal stem cells, and Notch targets were not derepressed. We provide evidence that gamma-secretase-dependent but RBPj-independent Notch intracellular domain activity operating in the first hair follicles is responsible for a delay in follicular destruction, which results in lower serum thymic stromal lymphopoietin levels, milder B-cell lymphoproliferative disease, and improved survival in Msx2-Cre(+/tg);Rbpj(f/f) mice. Minimal amounts of the Notch intracellular domain were sufficient for rescue, which was not mediated by transcription, suggesting that the Notch intracellular domain is acting through a novel mechanism. |