Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity

Krishnanand Padmanabhan, Hanna Grobe, Jonathan Cohen, Arad Soffer, Adnan Mahly, Orit Adir, Ronen Zaidel-Bar, Chen Luxenburg

Research output: Contribution to journalArticlepeer-review

Abstract

Planar cell polarity (PCP) is essential for tissue morphogenesis and homeostasis; however, the mechanisms that orchestrate the cell shape and packing dynamics required to establish PCP are poorly understood. Here, we identified a major role for the globular (G)-actin-binding protein thymosin-β4 (TMSB4X) in PCP establishment and cell adhesion in the developing epidermis. Depletion of Tmsb4x in mouse embryos hindered eyelid closure and hair-follicle angling owing to PCP defects. Tmsb4x depletion did not preclude epidermal cell adhesion in vivo or in vitro; however, it resulted in abnormal structural organization and stability of adherens junction (AJ) due to defects in filamentous (F)actin and G-actin distribution. In cultured keratinocytes, TMSB4X depletion increased the perijunctional G/F-actin ratio and decreased G-actin incorporation into junctional actin networks, but it did not change the overall actin expression level or cellular F-actin content. A pharmacological treatment that increased the G/F-actin ratio and decreased actin polymerization mimicked the effects of Tmsb4x depletion on both AJs and PCP. Our results provide insights into the regulation of the actin pool and its involvement in AJ function and PCP establishment.

Original languageEnglish
Article numberdev193425
JournalDevelopment (Cambridge)
Volume147
Issue number23
DOIs
StatePublished - Dec 2020

Keywords

  • Actin cytoskeleton
  • Adherens junctions
  • Epidermis
  • Morphogenesis
  • Planar cell polarity

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