Sergei Y. Sokol

Research

Cell polarity in vertebrate development, neural development, axis specification, Wnt signaling, morphogenetic movements

Polarity is a fundamental cell property that is essential for cell functions and is required for cell maintenance and differentiation. In embryonic development, cell polarity is reflected in asymmetric division of stem cell progenitors and developmental fate decisions. The frog Xenopus laevis makes an important in vivo vertebrate system to study cell polarity in various developmental contexts. Using both frog and mouse embryos, we are studying biochemical mechanisms that generate cell and tissue polarity. Our group would like to understand how developmental polarity is acquired and how communication between embryonic cells leads to their differentiation and assembly into specific tissues.

Several aspects of cell polarity and fate are controlled by the secreted growth factors of the Wnt family that are related to the proto-oncogene Wnt1. Our previous work demonstrated the structural and functional conservation of the Wnt pathway in vertebrates during formation of the Spemann organizer, a special signaling center in the embryo responsible for neural induction and head development. In vertebrate embryos, Wnt proteins are responsible for dorso-ventral and antero-posterior axis polarity, cell proliferation and cell death. Consistent with their important roles, many components of the canonical Wnt pathway are mutated in colon carcinomas, melanomas, liver, breast and skin tumors. In addition, Wnt signaling regulates morphogenetic cell movements and accompanying cytoskeletal changes during gastrulation. Since this pathway is distinct from the canonical beta-catenin pathway, we want to learn how different proteins relay Wnt signals to different targets.

In embryonic development, different cell types often differentiate as a result of asymmetric division of stem/progenitor cells. The apical Par protein complex, consisting of the PDZ-containing proteins Par-6 and Par-3 and atypical protein kinase C (aPKC), functions to control asymmetric divisions and establish cell polarity in a variety of cell types. The basolateral determinants PAR-1 and Lgl play equally important roles at the opposite side of epithelial cells. These proteins are highly conserved from worms to humans and function to regulate cell polarity in many embryonic tissues. Our studies demonstrate that Lgl is required for cell polarity and asymmetric cell division during primary neurogenesis in Xenopus ectoderm and its localization may be controlled by Wnt signaling. We are using the cell biological and embryological approaches in the frog Xenopus laevis and the advantages of the genetic approach in mice to study cell polarity and asymmetric division of neural progenitor cells. We would like to learn how the subcellular localization of Lgl and Par proteins regulates the self-renewal and differentiation of neural stem/progenitor cells. The knowledge of molecular mechanisms regulating neuronal differentiation should have implications on stem cell research and regenerative medicine.

For more information, please visit the Sokol Laboratory website.