All Publications


  • Context matters: Lessons in epithelial polarity from the Caenorhabditis elegans intestine and other tissues. Current topics in developmental biology Naturale, V. F., Pickett, M. A., Feldman, J. L. 2023; 154: 37-71

    Abstract

    Epithelia are tissues with diverse morphologies and functions across metazoans, ranging from vast cell sheets encasing internal organs to internal tubes facilitating nutrient uptake, all of which require establishment of apical-basolateral polarity axes. While all epithelia tend to polarize the same components, how these components are deployed to drive polarization is largely context-dependent and likely shaped by tissue-specific differences in development and ultimate functions of polarizing primordia. The nematode Caenorhabditis elegans (C. elegans) offers exceptional imaging and genetic tools and possesses unique epithelia with well-described origins and roles, making it an excellent model to investigate polarity mechanisms. In this review, we highlight the interplay between epithelial polarization, development, and function by describing symmetry breaking and polarity establishment in a particularly well-characterized epithelium, the C. elegans intestine. We compare intestinal polarization to polarity programs in two other C. elegans epithelia, the pharynx and epidermis, correlating divergent mechanisms with tissue-specific differences in geometry, embryonic environment, and function. Together, we emphasize the importance of investigating polarization mechanisms against the backdrop of tissue-specific contexts, while also underscoring the benefits of cross-tissue comparisons of polarity.

    View details for DOI 10.1016/bs.ctdb.2023.02.007

    View details for PubMedID 37100523

  • Separable mechanisms drive local and global polarity establishment in the C. elegans intestinal epithelium. Development (Cambridge, England) Pickett, M. A., Sallee, M. D., Cote, L., Naturale, V. F., Akpinaroglu, D., Lee, J., Shen, K., Feldman, J. L. 2022

    Abstract

    Apico-basolateral polarization is essential for epithelial cells to function as selective barriers and transporters, and to provide mechanical resiliency to organs. Epithelial polarity is established locally, within individual cells to establish distinct apical, junctional, and basolateral domains, and globally, within a tissue where cells coordinately orient their apico-basolateral axes. Using live imaging of endogenously tagged proteins and tissue specific protein depletion in the C. elegans embryonic intestine, we found that local and global polarity establishment are temporally and genetically separable. Local polarity is initiated prior to global polarity and is robust to perturbation. PAR-3 is required for global polarization across the intestine but is not required for establishment of local polarity as small groups of cells are able to establish polarized domains in PAR-3 depleted intestines in an HMR-1/E-cadherin dependent manner. Despite the role of PAR-3 in localizing PKC-3 to the apical surface, we additionally find that PAR-3 and PKC-3/aPKC have distinct roles in the establishment and maintenance of local and global polarity. Together, our results indicate that different mechanisms are required for local and global polarity establishment in vivo.

    View details for DOI 10.1242/dev.200325

    View details for PubMedID 36264257

  • A Polarizing Issue: Diversity in the Mechanisms Underlying Apico-Basolateral Polarization In Vivo. Annual review of cell and developmental biology Pickett, M. A., Naturale, V. F., Feldman, J. L. 2019

    Abstract

    Polarization along an apico-basolateral axis is a hallmark of epithelial cells and is essential for their selective barrier and transporter functions, as well as for their ability to provide mechanical resiliency to organs. Loss of polarity along this axis perturbs development and is associated with a wide number of diseases. We describe three steps involved in polarization: symmetry breaking, polarity establishment, and polarity maintenance. While the proteins involved in these processes are highly conserved among epithelial tissues and species, the execution of these steps varies widely and is context dependent. We review both theoretical principles underlying these steps and recent work demonstrating how apico-basolateral polarity is established in vivo in different tissues, highlighting how developmental and physiological contexts play major roles in the execution of the epithelial polarity program. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 35 is October 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

    View details for DOI 10.1146/annurev-cellbio-100818-125134

    View details for PubMedID 31461314