How the Heart Takes Form (2/11/2008)

Heart formation in the zebrafish: Transition of the flat, disc-shaped heart field into the primary linear heart tube, which then evolves into a multi-chamber, hollow organ. - Graphics: Stefan Rohr

For the first time, scientists have described the transition of the flat, disc-shaped heart field into the primary linear heart tube. The investigations on zebrafish embryos were made by Stefan Rohr and Cécile Otten, members of the research group of Dr. Salim Abdelilah-Seyfried of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany. The research results of the developmental biologists have just been published in the online edition of Circulation Research*.

Currently, one of the most important areas to explore in developmental biology is how cellular transformation processes lead to the three-dimensional formation (morphogenesis) of organs. A better understanding of these processes is a basic requirement for elucidating congenital malformation of organs.

The heart, for instance, develops in the embryo from a flat disc, the so-called heart field. The tissue of this two-dimensional structure consists of a thin layer of epithelial cells. Similar cells line all inner organs, but also the skin and blood vessels.

Which cellular processes drive the formation of the three-dimensional heart tube that then evolves into a multi-chamber, hollow organ? Do individual cells migrate and form this hollow structure by fusing with other cells or does the whole heart field change its form? Until now, all of these were open questions in developmental biology.

Stefan Rohr, PhD student with Dr. Abdelilah-Seyfried, used zebrafish (Latin: Danio rerio) for his investigations because their embryos are transparent, allowing researchers to observe each cell of the living organism under the microscope. That is why these vertebrates are particularly interesting for developmental biologists.

Surprisingly, the cells of the right and left heart fields behave very differently, as Stefan Rohr was able to demonstrate. The cells of the right heart field form a kind of lip which, as a group, migrates underneath the cells of the left heart field, thereby "involuting" or turning on its own axis once again. This complex inversion of the right heart field generates the ventral floor, whereas the noninvoluting left heart field gives rise to the future roof of the heart tube.

This process is steered by various genes, which also regulate the right/left asymmetry of vertebrates. When the researchers switched off one of these genes, the cells often migrated in the wrong direction and the lip was formed in the wrong place.

Note: This story has been adapted from a news release issued by Max-Delbrück-Centrum für Molekulare Medizin

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