V. Lecaudey: Role of the tight junction-associated protein Amotl2a in regulating the Hippo pathway and the size of the posterior lateral line primordium in zebrafish

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Principal investigator

Prof. Dr. Virginie Lecaudey

University of Frankfurt
 
 

Max-von-Laue-Str. 13
60438 Frankfurt (Main)

Tel: +49 (0)69-798-42102 (office)

lecaudey(at)bio.uni-frankfurt.de

Homepage

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SPP funded collaborator

Constanze Heinzen

University of Frankfurt
 
Developmental Biology of Vertebrates

Max-von-Laue-Str. 13
60438 Frankfurt (Main)

Tel: +49 (0)69-798-42106 (office)

heinzen(at)bio.uni-frankfurt.de

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SPP funded collaborator

Alicia Lardennois

University of Frankfurt
 
Developmental Biology of Vertebrates

Max-von-Laue-Str. 13
60438 Frankfurt (Main)

Tel: +49 (0)69-798-42106 (office)

lardennois(at)bio.uni-frankfurt.de

Summary

Control of organ size is a crucial aspect of embryonic development and homeostasis. Yet how cells sense when an organ has reached its final size and limit its growth is far from being understood. The Hippo signaling pathway plays a fundamental role in this control. When Hippo signaling is active, the downstream effectors Yap and Taz get phosphorylated and retained in the cytosol. In contrast, when Hippo signaling is inactive, Yap and Taz can translocate into the nucleus and activate the transcription of genes promoting proliferation and survival. Recently, the junction-associated proteins of the Motin family have been shown to inhibit Yap/Taz independent of the core kinase cascade.
The lateral line (LL) of zebrafish is a very powerful model to study epithelial morphogenesis. The LL primordium (LLP) is a group of about 100 adherent cells that collectively migrate on both sides of the fish embryo. As they migrate, cells change their shape to form cell clusters that are then deposited and differentiate into mechanosensory organs. In this project, we use this system to understand how tissue growth is controlled. We recently showed that loss of the Motin protein Amotl2a leads to an inc
rease in proliferation, and thus in the size of the LLP. This growth-limiting function is mediated by the Hippo pathway effector Yap1, with which Amotl2a physically interacts, and the Wnt/β-catenin effector Lef1. Since Motin proteins are also known to interact with junction complexes and with the actin cytoskeleton, they are good candidates to be implicated in the response of cells to mechanical forces. The main goal of our project is to investigate whether Amotl2a acts as a sensor of changes in cell density or cell shape to control proliferation and growth.

Expertise

Use of zebrafish as a model organism; Live imaging; Generation of zebrafish mutants and genome editing using TALEN and Cas9/Crispr