Proper skin and hair development are crucial for human health and emotional well-being. Having a thorough understanding of these processes and the mechanisms that govern them will aid in developing treatments for many diseases. During hair morphogenesis, epidermal progenitors integrate molecular 'instructions' emanating from the underlying dermal papillae (DP) with cell-autonomous signals, leading to de novo formation of hair follicles (HFs). Despite extensive efforts, our understanding of the epithelial- mesenchymal interactions that lead to HF development remain incomplete. Recently, microRNAs have been implicated in many important processes in development, including skin and HF morphogenesis. The miR-200 family has been shown to regulate epithelial-to-mesenchymal transition (EMT) in epithelial cancers, and preliminary in situ hybridization data shows that they are up-regulated at the leading edge of HFs, making them a promising candidate for regulating HF morphogenesis.
The first aim of this project entails determining the cell-autonomous role of miR-200s in the regulation of migration and proliferation of keratinocytes, which will be accomplished through the manipulation of miR-200s' levels in cultured keratinocytes.
The second aim of the proposed research involves determining the role of miR-200s in regulating epithelial-mesenchymal interactions during HF morphogenesis. Using a transgenic mouse over-expressing miR-200s specifically in the epidermis and hair follicle, the effects of miR-200s over-expression on HF morphogenesis will be examined through morphological analysis. The third and final aim of this research is to identify in vivo targets of miR-200 family members in the leading edge of the HF. FACS purification will be combined with a well-established miRNA target identification pipeline to identify miR-200s' specific targets in the leading edge of the HF. The combination of in vitro and in vivo studies proposed will contribute greatly to understanding the role of miR- 200s during HF morphogenesis. In addition, identifying targets of miR-200s will be crucial for elucidating their function. A more thorough understanding of miR-200 family function in murine skin and HFs will aid in our general understanding of skin and HF development, which will be crucial for developing therapies for many diseases.
Proper skin and hair follicle development are crucial for human health and emotional well-being. As such, understanding how these processes occur will aid in the development of treatments for many diseases. Our goal is to understand how microRNAs, a class of small RNAs with known regulatory roles in development and diseases, contribute to proper skin and hair follicle development.
| Hoefert, Jaimee E; Bjerke, Glen A; Wang, Dongmei et al. (2018) The microRNA-200 family coordinately regulates cell adhesion and proliferation in hair morphogenesis. J Cell Biol 217:2185-2204 |
