| First Author | Gu LH | Year | 2008 |
| Journal | Am J Pathol | Volume | 173 |
| Issue | 3 | Pages | 752-61 |
| PubMed ID | 18688029 | Mgi Jnum | J:139587 |
| Mgi Id | MGI:3808940 | Doi | 10.2353/ajpath.2008.071089 |
| Citation | Gu LH, et al. (2008) Hedgehog signaling, keratin 6 induction, and sebaceous gland morphogenesis: implications for pachyonychia congenita and related conditions. Am J Pathol 173(3):752-61 |
| abstractText | Keratins 6a and b (K6a, K6b) belong to a subset of keratin genes with constitutive expression in epithelial appendages, and inducible expression in additional epithelia, when subjected to environmental challenges or disease. Mutations in K6a or K6b cause a broad spectrum of epithelial lesions that differentially affect nail, hair, and glands in humans. Some lesions reflect a loss of the structural support function shared by K6, other keratins, and intermediate filament proteins. The formation of sebaceous gland-derived epithelial cysts does not fit this paradigm, raising the question of the unique functions of different K6 isoforms in this setting. Here, we exploit a mouse model of constitutively expressed Gli2, a Hedgehog (Hh) signal effector, to show that K6a expression correlates with duct fate in sebaceous glands (SGs). Whether in the setting of Gli2 transgenic mice skin, which develops a prominent SG duct and additional pairs of highly branched SGs, or in wild-type mouse skin, K6a expression consistently coincides with Hh signaling in ductal tissue. Gli2 expression modestly transactivates a K6a promoter-driven reporter in heterologous systems. Our findings thus identify K6 as a marker of duct fate in SGs, partly in response to Hh signaling, with implications for the pathological expansion of SGs that arises in the context of certain keratin-based diseases and related disorders. |
