Serum Response Factor Controls Transcriptional Network Regulating Epidermal Function and Hair Follicle Morphogenesis
| Autor: | Anna Hindes, Miroslav Blumenberg, Seth D. Crosby, Alexi Kiss, Narendrakumar Ramanan, Frode L. Jahnsen, Carole J. Burns, Tatiana Efimova, Liang Ma, Denis Khnykin, Yan Yin, Aaron C. Koppel, Congxing Lin |
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| Rok vydání: | 2013 |
| Předmět: |
Keratinocytes
Serum Response Factor Cell type Transcription Genetic genetic structures Mice Nude Cell Communication Dermatology Biology Biochemistry Mice Serum response factor Morphogenesis medicine Animals Cytoskeleton Transcription factor Molecular Biology Cell Proliferation Mice Knockout integumentary system Cell Biology Hair follicle Phenotype eye diseases Cell biology Hair follicle morphogenesis medicine.anatomical_structure Models Animal Immunology embryonic structures Female sense organs Epidermis Keratinocyte Hair Follicle Signal Transduction Transcription Factors |
| Zdroj: | Journal of Investigative Dermatology. 133(3):608-617 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2012.378 |
| Popis: | Serum response factor (SRF) is a transcription factor that regulates the expression of growth-related immediate-early, cytoskeletal, and muscle-specific genes to control growth, differentiation, and cytoskeletal integrity in different cell types. To investigate the role for SRF in epidermal development and homeostasis, we conditionally knocked out SRF in epidermal keratinocytes. We report that SRF deletion disrupted epidermal barrier function leading to early postnatal lethality. Mice lacking SRF in epidermis displayed morphogenetic defects, including an eye-open-at-birth phenotype and lack of whiskers. SRF-null skin exhibited abnormal morphology, hyperplasia, aberrant expression of differentiation markers and transcriptional regulators, anomalous actin organization, enhanced inflammation, and retarded hair follicle (HF) development. Transcriptional profiling experiments uncovered profound molecular changes in SRF-null E17.5 epidermis and revealed that many previously identified SRF target CArG box-containing genes were markedly upregulated in SRF-null epidermis, indicating that SRF may function to repress transcription of a subset of its target genes in epidermis. Remarkably, when transplanted onto nude mice, engrafted SRF-null skin lacked hair but displayed normal epidermal architecture with proper expression of differentiation markers, suggesting that although keratinocyte SRF is essential for HF development, a cross-talk between SRF-null keratinocytes and the surrounding microenvironment is likely responsible for the barrier-deficient mutant epidermal phenotype. |
| Databáze: | OpenAIRE |
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