Thymosin β4 (TMSB4X) is a G-actin-binding protein that has been shown to regulate G-actin distribution and, in some contexts, promote F-actin polymerisation. In vivo, its depletion disrupts cell migration and differentiation in the heart and impairs hair growth in the epidermis. Chen Luxenburg and colleagues now set out to further investigate the role of TMSB4X in the developing skin. They knock down Tmsb4x levels in the skin through in utero delivery of short hairpin RNAs, and identify defects in eyelid closure and in hair follicle orientation – both phenotypes associated with disrupted planar cell polarity (PCP) signalling. Consistent with this, polar localisation of CELSR1, a core PCP protein, is impaired upon Tbsb4x knockdown. The authors go on to uncover defects in adherens junction and peripheral F-actin distribution both in vivo and in primary keratinocyte culture. They provide evidence that TMSB4X is required for G-actin incorporation into peripheral actin networks and for adherens junction stability. These insights into the molecular and cellular mechanisms by which this G-actin-binding protein regulates skin development are particularly important given that TMSB4X peptides are in clinical trials for treatment of a number of skin conditions.
