The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation
| Autor: | Alexander Awgulewitsch, John P. Sundberg, Mary Ann Baybo, Ron L. Peterson, Nathanael D. Pruett, Kathleen A. Potter, Christopher S. Potter, Michael J. Kern, Alan R. Godwin |
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| Rok vydání: | 2010 |
| Předmět: |
Keratinocytes
Hoof and Claw Cellular differentiation Mutant Down-Regulation Mice Nude Dermatology Biology Transfection Biochemistry Hair keratin Article 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Hox gene Molecular Biology 030304 developmental biology Homeodomain Proteins 0303 health sciences integumentary system FOXN1 Gene Expression Regulation Developmental Cell Differentiation Forkhead Transcription Factors Cell Biology Hair follicle Molecular biology Mice Mutant Strains Mice Inbred C57BL medicine.anatomical_structure 030220 oncology & carcinogenesis Homeobox Chromatin immunoprecipitation Hair Follicle Biomarkers |
| Zdroj: | The Journal of investigative dermatology. 131(4) |
| ISSN: | 1523-1747 |
| Popis: | Among the Hox genes, homeobox C13 (Hoxc13) has been shown to be essential for proper hair shaft differentiation, as Hoxc13 gene-targeted (Hoxc13(tm1Mrc)) mice completely lack external hair. Because of the remarkable overt phenotypic parallels to the Foxn1(nu) (nude) mutant mice, we sought to determine whether Hoxc13 and forkhead box N1 (Foxn1) might act in a common pathway of hair follicle (HF) differentiation. We show that the alopecia exhibited by both the Hoxc13(tm1Mrc) and Foxn1(nu) mice is because of strikingly similar defects in hair shaft differentiation and that both mutants suffer from a severe nail dystrophy. These phenotypic similarities are consistent with the extensive overlap between Hoxc13 and Foxn1 expression patterns in the HF and the nail matrix. Furthermore, DNA microarray analysis of skin from Hoxc13(tm1Mrc) mice identified Foxn1 as significantly downregulated along with numerous hair keratin genes. This Foxn1 downregulation apparently reflects the loss of direct transcriptional control by HOXC13 as indicated by our results obtained through co-transfection and chromatin immunoprecipitation (ChIP) assays. As presented in the discussion, these data support a regulatory model of keratinocyte differentiation in which HOXC13-dependent activation of Foxn1 is part of a regulatory cascade controlling the expression of terminal differentiation markers. |
| Databáze: | OpenAIRE |
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