A Scribble/Cdep/Rac pathway controls follower-cell crawling and cluster cohesion during collective border-cell

Joseph P Campanale¹, James A Mondo¹, Denise J Montell¹

¹Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.

|November 8, 2022

Summary

This study explores how cells in a group move together during development. Using fruit flies, the researchers found that a specific pathway involving proteins called Scribble, Cdep, and Rac helps follower cells move and stay together. They discovered that Cdep activates Rac, which is important for cell movement. Scribble and related proteins control where Cdep is located in the cell. When Cdep is moved to a new location, it can partially fix problems caused by losing Scribble. This pathway is essential for coordinated cell migration and could apply to other biological processes.

Area of Science:

Cell migration mechanisms in developmental biology
Molecular signaling in Drosophila model systems
Collective cell movement in epithelial tissues

Background:

Collective cell migration is essential for tissue morphogenesis and disease progression. Drosophila border cells serve as a model for studying this process. Prior research has shown that leading cells use Rac to drive protrusions. However, the role of Rac in follower cells remains unclear. No prior work had resolved how follower cells maintain cluster cohesion. This gap motivated investigations into downstream effectors of Rac. Basolateral proteins like Scribble are known to regulate cell polarity. Their connection to Rac activity in follower cells had not been established. This study aims to clarify the regulatory pathway in follower cells.

Purpose Of The Study:

The study aimed to determine how follower cells maintain motility and cluster cohesion during collective migration. Border-cell clusters consist of leaders and followers, with distinct roles. The authors sought to identify upstream regulators of Rac in followers. They hypothesized that a specific pathway might coordinate movement. Basolateral polarity proteins were considered potential regulators. Cdep was proposed as a candidate guanine nucleotide exchange factor. The role of Scribble in this context was also explored. This approach could reveal mechanisms of collective cell migration.

Main Methods:

The researchers used Drosophila border-cell migration as a model system. They analyzed the role of Rac in follower-cell motility. Cdep was identified as a Rac guanine nucleotide exchange factor. Genetic knockdown and relocalization experiments were performed. Fluorescent tagging of Cdep (Cdep::GFP) allowed tracking of localization. Scribble, Discs large, and Lethal giant larvae were studied for co-localization. Phenotypic analysis compared effects of Scribble and Cdep disruption. The study combined genetic manipulation with live imaging techniques.

Main Results:

All border cells require active Rac for motility and cluster cohesion. Cdep was identified as a key regulator of follower-cell migration. Cdep promotes cell crawling and maintains cluster compactness. Scribble and related proteins localize Cdep basolaterally. Cdep relocalization partially rescues Scribble knockdown effects. This suggests Cdep is a major downstream effector of Scribble. The Scrib/Cdep/Rac pathway coordinates collective migration. These findings highlight a conserved mechanism in cell movement.

Conclusions:

The study concludes that a Scrib/Cdep/Rac pathway regulates follower-cell migration. This pathway is essential for cell crawling and cluster cohesion. Cdep acts downstream of basolateral polarity proteins. The findings suggest a conserved mechanism in collective migration. The role of Cdep in follower cells was previously unknown. The study supports a model where polarity proteins regulate Rac activity. This pathway may apply to other migratory cell types. The results provide a framework for future studies on cell migration.

Keywords:

Cdep FARP2 Rac1 RhoGTPases Scribble complex apicobasal polarity border cells collective cell migration par complex cell migration mechanisms Drosophila border cells Rac GTPase function collective cell movement

Frequently Asked Questions

The pathway promotes follower-cell crawling and cluster cohesion during collective migration.

Cdep acts as a Rac guanine nucleotide exchange factor, promoting cell motility.

Cdep's basolateral localization is regulated by Scribble, which is crucial for its function in follower cells.

Cdep relocalization partially rescues Scribble knockdown effects, suggesting a functional link.

The pathway maintains cluster cohesion by regulating follower-cell motility and positioning.

The study identifies a conserved mechanism that coordinates cell movement in migratory clusters.

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