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Welcome to the SOKOL laboratory

Department of Cell, Developmental and Regenerative Biology

Icahn School of Medicine at Mount Sinai

 

Wnt signaling and cell polarity in vertebrate embryo development

We study how various signaling pathways together with physical forces regulate cell fate determination and cell polarity in embryonic development. Our past experiments revealed an essential role for the Wnt pathway in vertebrate axis determination and uncovered its equally important function in morphogenetic movements during gastrulation and neurulation (Sokol et al., 1991; Sokol, 1996). More recently, we have been investigating cross-talk of apical-basal and planar cell polarity (PCP) proteins in vertebrate ectoderm, using Xenopus and mammalian progenitor models (Dollar et al., 2005; Lake and Sokol, 2009; Chuykin et al., 2018, Chuykin et al., 2021). We are now developing new technologies based on proximity biotinylation and live imaging to understand the interplay of mechanotransduction and biochemical signaling underlying apical constriction and neural tube closure in vertebrate embryos.  These studies aim to define how Wnt and PCP signaling pathways contribute to actomyosin dynamics in epithelial cells and tissue morphogenesis.  Other projects explore roles of centrosomes and cilia in neural crest and skin differentiation and investigate cross-talk between Wnt, FGF and less studied embryonic signaling pathways (Itoh et al., 2021; Reis and Sokol, 2021).

The interplay of biochemical signals and mechanical forces  in morphogenesis  

We are interested in the molecular and cellular mechanisms by which embryonic cells and tissues respond to mechanical forces during morphogenesis. Mechanotransduction is known as a process, by which a mechanical cue is sensed by a molecular component of the cell, converted to a biochemical signal and used to affect various biological processes, from cell migration to cell lineage specification.  Our group has been studying how changes in cell polarity determine collective cell behaviors during gastrulation and neurulation. To approach this problem, we are focusing on the core planar cell polarity (PCP) pathway that is one of the main drivers of morphogenetic processes in vertebrates. The core PCP proteins (Vang/Vang-like, Prickle/Pk, Dishevelled/Dvl, Frizzled/Fz and Flamingo/Celsr) have been discovered in Drosophila genetic studies and shown to be structurally and functionally conserved in many animals. In vertebrates, core PCP protein complexes accumulate at opposite cell edges along the anteroposterior body axis, marking axial polarity. The significance of the core PCP proteins extends far beyond being cell polarity markers, as their vertebrate homologs function in key developmental processes, including gastrulation movements, neural tube closure, branching morphogenesis, formation of functional cilia and left-right patterning.  How PCP proteins coordinate collective cell behaviors remains a challenging mystery that has been occupying scientists for almost three decades.

Our recent work 1) has shown that PCP is induced by localized embryonic signals (Mancini et al., 2021), 2) demonstrated a new feedback regulation between Fz3 and Vangl2 (Chuykin et al., 2021), 3) identified Wtip, Shroom3 and LMO7 as candidate molecules that link core PCP complexes to actomyosin contractions that drive many morphogenetic events, such as apical constriction (Chu et al., 2018, Matsuda et al., 2021)We continue to investigate a) how cells polarize in response to a cue, b) how the cell polarity translates into spatially restricted activation of Myosin II, and c) how actomyosin contractions alter cell shape and coordinate collective cell movements.

The questions we ask :

  • What mechanisms regulate asymmetric division and fate in stem cells?
  • How do secreted growth factors regulate cell polarity and cell shape?
  • How do mechanical forces instruct biochemical signaling in vertebrate embryos and vice versa?
  • How is planar cell polarity (PCP) established in the neural plate?
  • How does planar polarity influence cell movements and cell fates?

Contact us or inquire about research opportunities by writing to sergei.sokol@mssm.edu