Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 608-617 |
Number of pages | 10 |
Journal | Journal of Investigative Dermatology |
Volume | 133 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2013 |
Funding
We thank Raphael Kopan, Jeffrey H. Miner, and Shadmehr Demehri for helpful discussions and critical reading of the manuscript; Meei-Hua Lin for helpful discussions and technical advice; and Erin L. Gribben for mouse husbandry. This work was financially supported by the Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine (T Efimova).
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Dermatology
- Cell Biology