Control of Planar cell polarity and spindle positioning in C. elegans epithelial Seam Cells


Supervising PI

Sander van den Heuvel (website )

ESR 13 Janine Anselmo Cravo

Project description

Background

Cell-cell contacts are critical for epithelial polarity, proliferation control, and tissue or-ganization. While cell junctions contribute to contact inhibition of proliferation and cell division orientation in some epithelia, it remains unclear whether and how such roles exist in other systems. Here, we investigate the contribution of junctional contacts in the reproducible division pattern of the C. elegans skin precursor cells. These so-called “seam cells” form two lateral epithelia, are connected through apical junctions, show apical-basal as well as anterior-posterior polarity, and undergo a pattern of symmetric and asymmetric cell divisions dependent on Wnt/?-catenin asymmetry sig-naling.

Objectives

We sought to specifically disrupt seam cell adherens junctions, in order to investigate whether these contacts guide anterior-posterior tissue polarity and cell proliferation control.

Summary of Results

To disrupt seam cell adherens junctions, we used tissue-specific gene knockout and protein degradation of the E-cadherin homolog, HMR-1. This resulted in gaps in the seam cell row, and occasionally fully detached seam cells at later larval stages. The detached cells showed apparently normal division timing. However, the positioning of the mitotic spindle was occasionally abnormal, and based on a Wnt signaling readout, APR-1/APC, localization and cell fusion events, the detached cells showed frequent reversal or loss of tissue polarity and cell fate, in later development. Combined inactivation of HMR-1/E-cadherin and an additional junctional component, SAX-7/L1CAM, resulted in full seam cell detachment in early development. We will use this double knockout to further characterize the contribution of adhesive contacts and cellular shape in the control of tissue polarity and cell proliferation.

Publications

Anselmo-Cravo, J. and Van den Heuvel, S. (2019). Current opinion in cell biology. In Preparation