کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2175065 1093830 2007 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Epidermal hyperplasia and expansion of the interfollicular stem cell compartment in mutant mice with a C-terminal truncation of Patched1
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Epidermal hyperplasia and expansion of the interfollicular stem cell compartment in mutant mice with a C-terminal truncation of Patched1
چکیده انگلیسی

Hedgehog (Hh) signaling is conserved from flies to humans and is indispensable in embryogenesis and adulthood. Patched (Ptc) encodes a receptor for Hh ligands and functions as a tumor suppressor. PTCH1 mutations in humans are found in basal cell carcinoma (BCC) and irradiated Ptc1+/− mice recapitulate this phenotype. However, due to embryonic lethality associated with the Ptc1 null mutation, its normal function in embryonic and adult skin remains unknown. Here we describe the epidermal phenotypes of a spontaneous and viable allele of Ptc1, Ptc1mes, in which the C-terminal domain (CTD) is truncated. Ptc1mes/mes embryos display normal epidermal and hair follicle development. Postnatal Ptc1mes/mes skin displays severe basal cell layer hyperplasia and increased proliferation, while stratification of the suprabasal layers is mostly normal. Interestingly, truncation of the Ptc1 CTD did not result in skin tumors. However, long term labeling studies revealed a greater than three-fold increase in label-retaining cells in the interfollicular epidermis of Ptc1mes/mes adults, indicating possible expansion of the epidermal stem cell compartment. Increased expression of regulators of epidermal homeostasis, c-Myc and p63, was also observed in Ptc1mes/mes adult skin. These results suggest that the CTD of Ptc1 is involved in regulating epidermal homeostasis in mature skin.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Biology - Volume 308, Issue 2, 15 August 2007, Pages 547–560
نویسندگان
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