Biology subjects

Ventrella, R.

Publications and source records attributed to Ventrella, R..

2 recordsLinked to original sources

bioRxiv2023

Bidirectional multiciliated cell extrusion is controlled by Notch driven basal extrusion and Piezo 1 driven apical extrusion.

Xenopus embryos are covered with a complex epithelium containing numerous multiciliated cells (MCCs). During late stage development there is a dramatic remodeling of the epithelium that involves the complete loss of MCCs. Cell extrusion is a well-characterized process for driving cell loss while maintaining epithelial barrier function. Normal cell extrusion is typically unidirectional whereas bidirectional extrusion is often associated with disease (e.g. cancer). We describe two distinct mechanisms for MCC extrusion, a basal extrusion driven by Notch signaling and an apical extrusion driven by Piezo1. Early in the process there is a strong bias towards basal extrusion, but as development continues there is a shift towards apical extrusion. Importantly, receptivity to the Notch signal is age-dependent and governed by the maintenance of the MCC transcriptional program such that extension of this program is protective against cell loss. In contrast, later apical extrusion is regulated by Piezo 1 such that premature activation of Piezo 1 leads to early extrusion while blocking Piezo 1 leads to MCC maintenance. Distinct mechansms for MCC loss underlie the importance of their removal during epithelial remodeling. Summay StatementCell extrusion typically occurs unidirectionally. We have identified a single population of multiciliated cells that extrudes bidirectionally: Notch-driven basal extrusion and Piezo 1-mediated apical extrusion.

cell biology↗

bioRxiv2021

Tubulin Acetylation Promotes Penetrative Capacity of Cells Undergoing Radial Intercalation

The post-translational modification of tubulin provides a wide diversity of differential functions to microtubule networks. Here we address the role of tubulin acetylation on the penetrative capacity of cells undergoing radial intercalation in the skin of Xenopus embryos. Radial intercalation is the process by which cells move apically and penetrate the epithelial barrier via inserting into the outer epithelium. As such there are two opposing forces that regulate the ability of cells to intercalate: the restrictive forces of the epithelial barrier versus the penetrative forces of the intercalating cell. By positively and negatively modulating tubulin acetylation specifically in the intercalating cells, the timing of intercalation can be altered such that cells with more acetylated microtubules penetrate the epithelium faster. Moreover, the Xenopus epithelium is a complex array of variable types of vertices and we find that intercalating cells preferentially penetrate at higher order "rosette" vertices as opposed to the more prevalent tricellular vertices. We observed differential timing in the ability of cells to penetrate different types of vertices, indicating lower order vertices represent more restrictive sites of insertion. Interestingly, we are able to shift the accessibility of early intercalating cells towards the more restrictive tricellular junctions by modulating the level of tubulin acetylation and the subsequent penetrative capacity of intercalating cells. Overall our data implicate tubulin acetylation in driving tissue penetration of intercalating cells.

cell biology↗