Research

Regulation of embryonic lineages by Wnt signaling

Our early studies assessed molecular processes underlying the formation of the dorsal signaling center, also known as the Spemann organizer.  This analysis revealed an essential role for secreted Wnt proteins in vertebrate axis determination.  Our group continued to study Wnt pathways for a number of years and obtained valuable insights related to several Wnt signaling components, from secreted Wnt antagonists and Frizzled receptors to transcription factors of the TCF family (Sokol et al., 1991; Sokol, 1996; Itoh et al., 2005; Hikasa et al, 2010).

Wnt signaling in the control of mophogenesis

Our group has uncovered an important function of noncanonical Wnt signaling in regulating convergent extension movements during vertebrate gastrulation and neurulation (Sokol, 1996, 2000).  This discovery served as a basis for subsequent molecular characterization of the Wnt/PCP pathway.  More recently, we linked Wnt/Planar cell polarity (PCP) signaling to apical constriction, another fundamental morphogenetic event that leads to embryonic tissue folding (Ossipova et al., 2014, 2015).

The establishment of apicobasal and planar cell polarity (PCP) in the embryonic ectoderm

We have established the involvement of apical-basal and planar cell polarity proteins in cell fate determination during epidermal differentiation, neurogenesis and neural crest development, using mouse, human and Xenopus progenitor models (Dollar et al., 2005; Ossipova et al., 2009; Lake and Sokol, 2009).  We have recently shown that Wnt proteins can direct PCP in the vertebrate neural plate (Chu and Sokol, 2016).  These studies provided insights into asymmetric neural progenitor divisions during neurogenesis, multiciliated cell differentiation in the epidermis and mechanistically connected PAR, Notch and Wnt signaling to PCP.

 

Planar cell polarity during neural tube closure

Planar cell polarity is presumed essential for neural tube foldingWe have established a new model for neural plate PCP along the anteroposterior axis and found that this polarity requires both Wnt and Myosin II/ROCK signaling.  We have also characterized a new mediolateral axis of PCP that is likely involved in the regulation of apical constriction in the neural plate.  Our results suggest the involvement of PCP proteins in radial cell intercalations during neural plate closure (Ossipova et al., 2014, 2015; Sokol, 2016).

 

Noncanonical signaling during neural crest specification

The neural crest (NC) is a population of stem-cell-like cells that form in vertebrate embryos at the neural plate border and migrate to diverse locations in the body to give rise to multiple cell types. NC-specific genes are activated by signaling interactions between the surrounding embryonic tissues, including the epidermis, neuroectoderm and underlying mesoderm.  During the same time period, premigratory NC progenitors restructure their cytoskeleton and cell junctions in a process known as epithelial-mesenchymal transition (EMT), which is a prerequisite for their migratory behavior.  We are studying how cell adhesion and cell shape changes during EMT are connected to NC specification (Ossipova and Sokol, 2011).

 

Prickle3 interacts with Wtip, a tension-sensitive protein

It has been proposed that planar polarity is sensitive to mechanical forces and functions to regulate early morphogenetic processes, such as gastrulation and neurulation.  We discovered that

Wtip, a Prickle3-interacting protein containing LIM domains, can sense Myosin II activity and intercellular tension (Chu et al., 2018).  Moreover, Wtip is localized in ectodermal cells in a very peculiar manner, by forming cytoplasmic aggregates or puncta opposing each other across the cell membrane as shown in the image.  This localization may indicate that neighboring cells mechanically communicate with each other through Wtip.