Fabienne Lescroart: Getting to the Heart of Cardiac Development

The heart is the first organ to form in the embryo. But how its cells specialize and how its tissue is organized is not fully understood. Passionate about genetics, Fabienne Lescroart came to quickly devote her research to this fundamental stage of development. Her goal? Understand congenital heart malformations and develop regenerative medicine.

The heart, which starts to beat even before fully formed, is an organ whose development is a source of fascination from the very first moments. It still holds many mysteries – mysteries to which Fabienne Lescroart* has devoted her career. The title of the project that enabled her to set up her own ATIP-Avenir program research team reflects her objective: Breaking the Heartcode. Using models that mimic early embryonic development, the researcher is studying how common progenitor cells differentiate into cardiac cells, and how they organize themselves in time and space into functional muscle. The aim of this research is to better understand not just the physiology of the heart but also some of its congenital malformations. It could also contribute to the development of regenerative cell therapy in cardiology.

From zebrafish to embryo

Lescroart got her passion for genetics from watching the annual Telethon, a French fund-raising event, on TV. After obtaining her high school diploma, she immediately embarked on a five-year senior diploma in genetics, which is very research-oriented. Her first internship was in New York, where she began studying cardiac development in zebrafish and building her expertise in embryology and genetics. « That was when I got really hooked on cardiac development, and decided to focus my dissertation on it, » recalls the researcher. In 2007, she joined the team of Margaret Buckingham, a renowned biologist in the field of developmental biology, at Institut Pasteur in Paris. « I was able to show that the same line of cell progenitors gives rise to both head muscle cells and heart cells. » An original discovery since these two tissues differ on the molecular level, but not as surprising as one would think: « Some genetic heart conditions are associated with functional difficulties, such as with smiling or swallowing. This link could have its origin in a common cell lineage, » she explains.

She then continued her work in Brussels, in Cédric Blanpain’s laboratory, focusing on an early stage of embryonic development that occurs in humans around 15 days after fertilization, at the time of gastrulation. « This is a decisive stage for the embryo, where the first cells, organized in sheets, evolve to start forming organs. » The researcher then observed that, from this very early period, the progenitor cells that give rise to the heart are not as plastic as expected: they are already quite specialized, destined to evolve towards one or other of the regions of the heart.

Lescroart then joined Stéphane Zaffran’s team, dedicated to heart tissue development biology, at the Marseille Medical Genetics unit directed by Nicolas Levy. Then, in 2019, the desire to carry out her projects led her to apply, and be selected, for the ATIP-Avenir program. Now leading her own team, she uses a mouse model that mimics human embryology quite well. She also uses mouse embryonic stem cells in vitro. « From gastrulation onwards, different factors play a role in the fate of the progenitor cells: genetic but also exogenous factors, such as molecular signals sent by the surrounding tissues. This research should make it possible to understand, for example, what will lead a progenitor to evolve into an atrial or ventricular cell. » The objective will then be to validate her results on human embryonic stem cells.

« The support of the ATIP-Avenir program allows me to lead my own projects – it’s a springboard for my future career. It has also given me the opportunity to recruit two post-doctoral students who I would like to support. Mentoring is very important to me. I was very well supervised throughout my own training: I want to pass on my passion for cardiac development and support young people in their desire to go into research, » concludes Lescroart.

Note:
*unit 1251 Inserm/Aix-Marseille Université, Heart development team, Marseille Medical Genetics Center