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

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.

Anillin governs mitotic rounding during early epidermal development

“…Similar results were obtained when ANLN binding partner, RhoA, was deleted in vitro and in vivo [55]. While numerous factors differentiate between physiological and non-physiological conditions, a striking difference exists in the mechanical environment [83] and in cell shape [6,14,16], both of which are known to impact on actin-based processes and the activity of motor proteins [84][85][86]. Moreover, our results also show that the conditions in which Anln KD 1 0 MK are cultured impact the execution of cytokinesis.…”

“…In the epidermis and in cultured keratinocytes, cellshape dynamics were shown to impact tissue architecture and cell fate [6,10,14,16,[56][57][58]. Because ANLN is a key regulator of the actin cytoskeleton, which regulates cell shape [59] [60], we asked whether ANLN loss-offunction epidermis exhibits early defects in cell shape.…”

“…The actin cytoskeleton is ideally situated to orchestrate tissue development and homeostasis due to its roles in mechanical, structural, and regulatory processes [5][6][7]. In the developing epidermis, actin and its binding proteins are essential for basement membrane (BM) organization, cell adhesion, cell polarity, cell shape, spindle orientation, and cell delamination, all of which are necessary for the establishment of the epidermis's structure and function [8][9][10][11][12][13][14][15][16][17]. In line, mutations in actin regulators were shown to play a role in common skin diseases that hinder epidermal structure and function such as psoriasis [18][19][20] and cancer [21,22].…”

Understanding of mouse and human bladder at single‐cell resolution: integrated analysis of trajectory and cell‐cell interactive networks based on multiple scRNA‐seq datasets

“…Cxcl14 and Grem2 consistently showed a pseudotime trait in all five mouse pan‐fibroblasts; previous studies displayed that the Cxcl14 axis in fibroblasts can interact with multiple cancer cells and acts as a multi‐modal stimulator with tumor‐supporting properties, 34 , 35 , 36 and the activation of Grem2 in fibroblasts would promote pulmonary fibrosis. 37 For the development of urothelial cells, TMSB4X was a top gene in all datasets regardless of the mouse or human tissue sources, depletion of TMSB4X would cause abnormal stability of adherence junction in epidermal cells, 38 and a developmental trajectory using single‐cell proteomics revealed TMSB4X significantly decreased during hair‐cell differentiation. 39 In addition, increasing expression of UPK2, UPK1A, and UPK3A (Figure 3B ) has been seen through all datasets in both mouse and human bladder.…”

Utilizing Developmentally Essential Secreted Peptides Such as Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State—New Directions in Anti-Aging Regenerative Therapies

“…As suggested, investigation of a molecule's pre-and postnatal expression may presumably provide significant information regarding its potential clinical utilization and appliance. According to the present and earlier literature, beta thymosins are widely expressed among various tissues such as the brain, kidneys, heart, skin, eyes and cell types of the body [73][74][75][76][77][78][79][80][81][82][83][84]. The first investigations were communicated by Lin and colleagues in 1990, when they presented significant mRNA expression of both TB10 and TB4 in the cortex and cerebellum [73].…”