Sox2 modulates the function of two distinct cell lineages in mouse skin

Marta H Lesko,Ryan R Driskell,Kai Kretzschmar,Stephen J Goldie,Fiona M Watt

doi:10.1016/j.ydbio.2013.08.004

Marta H Lesko, Ryan R Driskell + Show 3 more

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https://doi.org/10.1016/j.ydbio.2013.08.004

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Abstract

In postnatal skin the transcription factor Sox2 is expressed in the dermal papilla (DP) of guard/awl/auchene hair follicles and by mechanosensory Merkel cells in the touch domes of guard hairs. To investigate the consequences of Sox2 ablation in skin we deleted Sox2 in DP cells via Blimp1Cre and in Merkel cells via K14Cre. Loss of Sox2 from the DP did not inhibit hair follicle morphogenesis or establishment of the dermis and hypodermis. However, Sox2 expression in the DP was necessary for postnatal maintenance of awl/auchene hair follicles. Deletion of Sox2 via K14Cre resulted in a decreased number of Merkel cells but had no effect on other epithelial compartments or on the dermis. The reduced number of Merkel cells did not affect the number or patterning of guard hairs, nerve density or the interaction of nerve cells with the touch domes. We conclude that Sox2 is a marker of two distinct lineages in the skin and regulates the number of differentiated cells in the case of the Merkel cell lineage and hair follicle type in the case of the DP.

Highlights

The transcription factor Sox2 is involved in maintenance of the early, pluripotent stem cells of the eipiblast (Avilion et al, 2003) and in re-establishing pluripotency in postnatal cell types (Takahashi and Yamanaka, 2006)
In view of the key contributions of dermal papilla (DP) cells and Merkel cells to skin function and the observation that Sox2 is a marker of Skin Derived Precursors (SKPs), we have investigated the consequences of deleting Sox2 in the DP and Merkel cell compartments
Blimp1 was not detected in E13.5 skin (Fig. 1A and data not shown). It was expressed at the onset of hair follicle morphogenesis at E14.5 in the precursors of the dermal papillae of all types of hair follicle, including Sox2-positive DP (Fig. 1B, C, E–H), consistent with previous reports (Horsley et al, 2006; Robertson et al, 2007)

Summary

Introduction

The transcription factor Sox is involved in maintenance of the early, pluripotent stem cells of the eipiblast (Avilion et al, 2003) and in re-establishing pluripotency in postnatal cell types (Takahashi and Yamanaka, 2006). Sox is essential for central nervous system (CNS) development and maintenance of neural stem cells (Pevny and Nicolis, 2010). Sox is expressed in the dermal papilla cells of guard/awl/ auchene hair follicles (Driskell et al, 2009) and in the dermal sheath cells of some hair follicles (Laga et al, 2010). Dermal papillae are specialised clusters of fibroblasts at the base of each hair follicle that regulate follicle development and cycling via reciprocal signalling with the overlying epidermal cells (Millar, 2002; Driskell et al, 2011). Depletion of Sox2-positive DP cells prevents formation of awl/auchene hair follicles in skin n Corresponding author at: Centre for Stem Cells and Regenerative Medicine, King's College London, 28th Floor, Guy's Tower, London SE1 9RT, UK

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