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18.09.2019 News

How are tissues and organs formed?

Dr. Maximina Yun © CRTD

Researchers identify important molecular players for the formation of embryonic cell structures

Understanding the molecular mechanisms underlying the mesmerising transformation of a fertised egg into a complex organism is a key goal of developmental biology, and one driving extensive investigations. Different tissues and organs derive from three primordial germ layers: endoderm, mesoderm and ectoderm. How do they become specified, and how do they subsequently diversify to form different structures?

Researchers of the CRTD teamed up with international scientists to investigate this question together with international colleagues. In particular, they addressed the lateral plate mesoderm (LPM) - the germ layer that gives rise to the cardiovascular, blood, kidney and smooth muscle cell fates among others, and whose origin was poorly understood.

Through a combination of genetic tools and live imaging techniques, the scientists identified a small enhancer of the zebrafish-specific gene draculin (drl) capable of driving pan-LPM expression across evolutionarily distant species, including chicken, lamprey, ciona, amphioxus and axolotl. This enhancer allowed them to determine that the LPM emerges as a specific mesendoderm field, and to identify the key molecular players (EomesoderminA, FoxH1, MixL1 and Smad) that control the formation of this critical embryonic structure. Altogether, this work increases our understanding of the network that that drives the specification of the lateral plate mesoderm, and suggest that it constitutes an ancestral, highly conserved programme predating the first vertebrates.

These findings are significant in several ways. First, they provide new insights into how cells decide what they want to become in development. This is important, as defining the networks that drive mayor developmental transitions can help us understand the mechanisms driving the diversification of animal forms and thus evolutionary adaptations.

Second, they uncover molecular networks that could be harnessed in therapeutic and regenerative settings. Guiding the therapeutically relevant differentiation of cultured embryonic or induced pluripotent stem (iPS) cells towards the LPM-derived cardiovascular, hematopoietic, or renal cell fates remains challenging, yet the new insights provided by the study may help designing protocols to increase reprogramming efficiency. 

This work was co-authored by CRTD research group lead Dr Maximina Yun and her colleagues Dr Anna Czarkwiani and Dr Dunja Knapp. It was led by Prof Christian Mossiman (IMLS, University of Zurich, Switzerland).

Publication: Nature Communications, „A conserved regulatory program initiates lateral plate mesoderm emergence across chordates”

Research Dr Maximina Yun