Molecular mechanisms and developmental control of PAR polarity in animal embryos

The National Institute of General Medical Sciences awarded the University of Texas at Austin $270,208 on April 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to conduct research on molecular mechanisms and developmental control of PAR polarity in animal embryos.

The research resolves the network of protein-protein interactions that supports animal cell polarity and explores how this network responds to developmental signals. The work centers on an evolutionarily conserved protein kinase called APKC that localizes to one end of a polarized cell and dictates polarized cell behaviors. Using C. elegans early embryos as an experimental system, the investigators will employ innovative single-molecule measurement tools to discover mechanistic links between developmental signals and the polarity machinery. The central hypothesis is that developmental signals control cell polarity by altering the molecular complexes in which APKC resides. The research will elucidate mechanisms regulating APKC assembly into different complexes in the zygote, determine how polarity is entrained to cell-cell contacts in eight-cell embryos, and establish how translation of new protein components remodels the polarity system between these developmental stages.

The award is a Project Grant with a period of performance from April 1, 2026, through March 31, 2031. Work is performed in Austin, Texas. The University of Texas at Austin is a subsidiary of the University of Texas System.

Abstract

Cell polarity is a fundamental feature of eukaryotic cells, and must be coordinated between cells and regulated to allow for normal animal development and tissue homeostasis. Despite genetic identification of proteins involved in cell polarity and a large body of knowledge about their interactions in vitro, IT remains unclear how polarity proteins are organized into signaling complexes in cells. This lack of knowledge has prevented the field from understanding mechanisms of developmental control of polarity signaling in vivo. The long-term goal of the proposed research is to resolve the network of protein-protein interactions that supports animal cell polarity and to understand how this network can respond to developmental signals. To enable progress towards this goal, the applicants have developed innovative experimental tools that allow single-molecule measurements of native protein complex abundance in single cells. This project focuses on an evolutionarily conserved protein kinase, called apkc, that plays a central role in polarity by localizing to one end of a polarized cell and dictating polarized cell behaviors. The applicants will make use of the c. Elegans early embryo, in which cells reproducibly polarize in response to multiple spatial and temporal cues, to discover mechanistic links between developmental signals and the polarity machinery. The central hypothesis of this work is that developmental signals control cell polarity by altering the molecular complexes in which apkc resides. This hypothesis will be explored by elucidating mechanisms that regulate assembly of apkc into different complexes in the zygote; by determining how polarity is entrained to cell-cell contacts in 8-cell embryos; and by determining how translation of new protein components remodels the polarity system between these two stages. The work proposed in this application is significant because IT will reveal fundamental mechanisms controlling cell polarity, and because IT places these mechanistic studies in a developmental context. The proposed work is innovative, in the applicant's opinion, because IT uses novel experimental methods to perform biochemical, mechanistic studies in vivo. By studying the biochemical control of apkc in multiple cellular and developmental contexts in a single experimental system, this work will identify fundamental mechanisms of PAR polarity signaling and to learn how these mechanisms are deployed to achieve different outcomes during development.