Biology subjects

Sokol, S. Y.

Publications and source records attributed to Sokol, S. Y..

6 recordsLinked to original sources

bioRxiv2025

Mechanical cues organize planar cell polarity during vertebrate morphogenesis and embryonic wound repair

Planar cell polarity (PCP) is a phenomenon of coordinated cell orientation in many epithelia and is required for early morphogenetic events, such as vertebrate gastrulation or neural tube closure that place embryonic tissues in their proper locations. Known PCP complexes segregate to opposite edges of each cell due to regulatory feedback interactions, however, whether and how PCP is connected to the tension-sensing machinery has been elusive. Here we observed dynamic polarization of Afadin- and -Actinin-interacting protein (ADIP) in the epithelia adjacent to the involuting marginal zone and the folding neural plate of Xenopus embryos, suggesting that it is controlled by mechanical cues. Supporting this hypothesis, ADIP puncta relocated in response to the pulling forces of neighboring ectoderm cells undergoing apical constriction. Moreover, ADIP puncta rapidly polarized in embryos subjected to stretching and during embryonic wound healing. ADIP formed a mechanosensitive complex with the PCP protein Diversin that was distinct from known core PCP complexes and required for wound repair. We propose that mechanically controlled planar polarization of the ADIP-Diversin complex guides cell behaviors in normal morphogenesis and during wound healing. HighlightsO_LIADIP is a mechanosensing protein that is planar polarized together with Diversin in epithelia during morphogenesis and wound repair C_LIO_LIEpithelial wound healing redistributes ADIP-containing complexes towards the wound. C_LIO_LIADIP and Diversin are interdependent and form a complex regulating morphogenesis and wound healing C_LIO_LIPositive regulatory feedback between mechanical forces and PCP signaling drives morphogenesis C_LI

developmental biology↗

bioRxiv2024

Prickle2 regulates apical junction remodeling and tissue fluidity during vertebrate neurulation

The process of folding the flat neuroectoderm into an elongated neural tube depends on tissue fluidity, a property that allows epithelial deformation while preserving tissue integrity. Neural tube folding also requires the planar cell polarity (PCP) pathway. Here, we report that Prickle2 (Pk2), a core PCP component, increases tissue fluidity by promoting the remodeling of apical junctions (AJs) in Xenopus embryos. This Pk2 activity is mediated by the unique evolutionarily conserved Ser-Thr-rich region (STR) in the carboxyterminal half of the protein. Mechanistically, the effects of Pk2 require Rac1 and are accompanied by increased cadherin dynamics and destabilization of tricellular junctions, the hotspots of AJ remodeling. Notably, Pk2 depletion leads to the accumulation of mediolaterally oriented cells in the neuroectoderm, whereas the overexpression of Pk2 or Pk1 containing the Pk2-derived STR promotes cell elongation along the anteroposterior axis. We propose that Pk2-dependent regulation of tissue fluidity contributes to anteroposterior tissue elongation in response to extrinsic cues.

developmental biology↗

bioRxiv2023

Myocardin-related transcription factors regulate morphogenetic events in vertebrate embryos by controlling F-actin organization and apical constriction

Myocardin-related transcription factors (Mrtfa and Mrtfb), also known as megakaryoblastic leukemia proteins (Mkl1/MAL and Mkl2), associate with serum response factor (Srf) to regulate transcription in response to actin dynamics, however, the functions of Mrtfs in early vertebrate embryos remain largely unknown. Here we document the requirement of Mrtfs for blastopore closure at gastrulation and neural plate folding in Xenopus early embryos. Both stimulation and inhibition of Mrtf activity caused similar gross morphological phenotypes, yet the effects on F-actin distribution and cell behavior were different. Suppressing Mrtf-dependent transcription reduced overall F-actin levels and inhibited apical constriction during gastrulation and neurulation. By contrast, constitutively active Mrtf caused tricellular junction remodeling and induced apical constriction in superficial ectoderm. The underlying mechanism appeared distinct from the one utilized by known apical constriction inducers. We propose that the regulation of apical constriction is among the primary cellular responses to Mrtf. Our findings highlight a dedicated role of specific transcription factors, Mrtfs, in early morphogenetic processes.

developmental biology↗

bioRxiv2023

Mechanical control of neural plate folding by apical domain alteration

Vertebrate neural tube closure is associated with complex changes in cell shape and behavior, however, the relative contribution of these processes to tissue folding is not well understood. In this study, we evaluated morphology of the superficial cell layer in the Xenopus neural plate. At the stages corresponding to the onset of tissue folding, we observed the alternation of cells with apically constricting and apically expanding apical domains. The cells had a biased orientation along the anteroposterior (AP) axis. This apical domain heterogeneity required planar cell polarity (PCP) signaling and was especially pronounced at neural plate hinges. Vertex model simulations suggested that spatially dispersed isotropically constricting cells cause the elongation of their non-constricting counterparts along the AP axis. Consistent with this hypothesis, cell-autonomous induction of apical constriction in Xenopus ectoderm cells was accompanied by the expansion of adjacent non-constricting cells. Our observations indicate that a subset of isotropically constricting cells can initiate neural plate bending, whereas a tug-of-war contest between the force-generating and responding cells reduces its shrinking along the AP axis. This mechanism is an alternative to anisotropic shrinking of cell junctions that are perpendicular to the body axis. We propose that neural folding relies on PCP-dependent transduction of mechanical signals between neuroepithelial cells.

developmental biology↗

bioRxiv2021

Identification of SSX2IP/Msd1 as a Wtip-binding partner by targeted proximity biotinylation

Wilms tumor-1-interacting protein (Wtip) is a LIM-domain-containing adaptor that links cell junctions with actomyosin complexes and modulates actomyosin contractility and ciliogenesis in Xenopus embryos. The Wtip C-terminus with three LIM domains binds binds Shroom3 and modulates Shroom3-induced apical constriction in ectoderm cells. We found that the N-terminal domain localizes to the basal bodies in skin multiciliated cells, but its interacting partners remain largely unknown. Using a novel targeted proximity biotinylation approach with anti-GFP antibody attached to the biotin ligase BirA in the presence of GFP-Wtip-N, we identified SSX2IP as the candidate binding protein. SSX2IP, also known as Msd1 or ADIP, is a centriolar satellite protein that functions as a targeting factor for ciliary membrane proteins. Wtip physically associated with SSX2IP and the two proteins formed mixed spherical aggregates in overexpressing cells in a dose-dependent manner, in a process that resembles phase separation. These results suggest that the interaction between SSX2IP and Wtip is relevant to their functions at the centrosome and basal bodies. The described antibody targeting of biotin ligase should be applicable to other GFP-tagged proteins.

biochemistry↗

bioRxiv2020

Rspo2 inhibits TCF3 phosphorylation to antagonize Wnt signaling during vertebrate anteroposterior axis specification

The Wnt pathway activates target genes by controlling the {beta}-catenin-T-cell factor (TCF) transcriptional complex during embryonic development and cancer. This pathway can be potentiated by R-spondins, a family of proteins that bind RNF43/ZNRF3 E3 ubiquitin ligases and LGR4/5 receptors to prevent Frizzled degradation. Here we demonstrate that, during Xenopus anteroposterior axis specification, Rspo2 functions as a Wnt antagonist, both morphologically and at the level of gene targets and pathway mediators. Unexpectedly, the binding to RNF43/ZNRF3 and LGR4/5 was not required for the Wnt inhibitory activity. Moreover, Rspo2 did not influence Dishevelled phosphorylation in response to Wnt ligands, suggesting that Frizzled activity is not affected. Further analysis indicated that the Wnt antagonism is due to the inhibitory effect of Rspo2 on TCF3/TCF7L1 phosphorylation that normally leads to target gene activation. Consistent with this mechanism, Rspo2 anteriorizing activity has been rescued in TCF3-depleted embryos. These observations suggest that Rspo2 is a context-specific regulator of TCF3 phosphorylation and Wnt signaling.

developmental biology↗