Stem cell dynamics in sebaceous gland morphogenesis in mouse skin.

The hair follicle (HF) and the sebaceous gland (SG) constitute the two integral parts of the pilosebaceous unit and significantly contribute to the barrier function of mammalian skin. Considerable progress has been made in our understanding how HF formation is regulated. However, the development of the SG is poorly understood, both at the molecular and cellular level. Here, we investigate the process of SG morphogenesis and the dynamics of its cellular organisation in more detail. The spatial and temporal organisation of distinct stem and progenitor compartments was analysed during morphogenesis of the pilosebaceous unit in mouse tail epidermis. Our experiments reveal a dynamic expression pattern for diverse HF stem cell marker molecules including Sox9 and Lrig1. Surprisingly, Sox9 and Lrig1 are initially coexpressed by epidermal progenitor cells and are confined to different regions within the pilosebaceous unit when the specification of the sebocyte cell lineage takes place. We demonstrate that SG development at the distal part of the HF is driven by asymmetric cell fate decision of Lrig1 positive stem cells, whereas MTS24/Plet1 positive precursor cells seem not to play a role in this process. Importantly, our data clearly show that distinct stem and progenitor compartments are established at different time points of development. By studying the process of SG morphogenesis more precisely, we discovered that the two prominent SGs attached to one tail HF originate from one small cluster of sebocyte cells. Finally, we show regional specificity for HF patterning and spatio-temporal control of the underlying molecular signals initiating the development of the pilosebaceous unit.