The role of Rnd3 in keratinocytes

Begum, Shabana (2017). The role of Rnd3 in keratinocytes. University of Birmingham. Ph.D.

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Abstract

The skin is continuously being shed and therefore it is vital that it is renewed. Epidermal self-renewal is dependent on a population of keratinocyte stem cells (KSC) that reside in the basal layer. During epidermal regeneration, KSC divide asymmetrically giving rise to more stem cells as well as committed progenitors. Committed progenitors exit the cell cycle before going on to differentiate to form the highly resilient cells that make up the outermost layer. It is thought that committed progenitors and KSC are differentially regulated therefore allowing for such different behaviors.
Rnd3 is an atypical GTPase that is constitutively active and has been previously shown to regulate keratinocyte differentiation. However, the identification of the molecular mechanism is currently unknown.
The work presented here shows that Rnd3 depletion enriches for keratinocytes with a number of ‘stem-like’ phenotypes including reduced differentiation, reduced cell size, increased adhesion to ECM proteins and a deregulation of putative stem cell markers. Furthermore, using a quantitative proteomic approach, it can be seen that Rnd3 regulated the abundance of proteins involved in regulating stem cell function. This work proposes a function for Rnd3 in the regulation of key proteins involved keratinocyte differentiation and self-renewal.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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