Focal adhesions are essential to drive zebrafish heart valve morphogenesis

Felix Gunawan; Alessandra Gentile; Ryuichi Fukuda; Ayele Taddese Tsedeke; Vanessa Jiménez-Amilburu; Radhan Ramadass; Atsuo Iida; Atsuko Sehara-Fujisawa; Didier Y. R. Stainier

doi:10.1083/jcb.201807175

Focal adhesions are essential to drive zebrafish heart valve morphogenesis

Felix Gunawan, Alessandra Gentile, Ryuichi Fukuda, Ayele Taddese Tsedeke, Vanessa Jiménez-Amilburu, Radhan Ramadass, Atsuo Iida, Atsuko Sehara-Fujisawa, Didier Y. R. Stainier

SCMMS Denmark Hill

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

Abstract

Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell–ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin α5β1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.

Original language	English
Journal	Journal of Cell Biology
DOIs	https://doi.org/10.1083/jcb.201807175
Publication status	Published - 4 Mar 2019

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title = "Focal adhesions are essential to drive zebrafish heart valve morphogenesis",

abstract = "Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell–ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin α5β1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.",

author = "Felix Gunawan and Alessandra Gentile and Ryuichi Fukuda and {Taddese Tsedeke}, Ayele and Vanessa Jim{\'e}nez-Amilburu and Radhan Ramadass and Atsuo Iida and Atsuko Sehara-Fujisawa and Stainier, {Didier Y. R.}",

year = "2019",

month = mar,

day = "4",

doi = "10.1083/jcb.201807175",

language = "English",

journal = "Journal of Cell Biology",

issn = "0021-9525",

publisher = "Rockefeller University Press",

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TY - JOUR

T1 - Focal adhesions are essential to drive zebrafish heart valve morphogenesis

AU - Gunawan, Felix

AU - Gentile, Alessandra

AU - Fukuda, Ryuichi

AU - Taddese Tsedeke, Ayele

AU - Jiménez-Amilburu, Vanessa

AU - Ramadass, Radhan

AU - Iida, Atsuo

AU - Sehara-Fujisawa, Atsuko

AU - Stainier, Didier Y. R.

PY - 2019/3/4

Y1 - 2019/3/4

N2 - Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell–ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin α5β1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.

AB - Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell–ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin α5β1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.

U2 - 10.1083/jcb.201807175

DO - 10.1083/jcb.201807175

M3 - Article

SN - 0021-9525

JO - Journal of Cell Biology

JF - Journal of Cell Biology

ER -

Focal adhesions are essential to drive zebrafish heart valve morphogenesis

Abstract

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