A crowning achievement in understanding the development of the head – sciencedaily


Cranial Neural Crest Cells, or CNCCs, contribute to many more parts of the body than their humble name suggests. These remarkable stem cells not only form the major part of the skull and facial skeleton of all vertebrates, from fish to humans, but can also generate everything from gills to cornea. To understand this versatility, scientists at Gage Crump’s lab created a series of atlases over time to understand the molecular decisions by which CNCCs engage in forming specific tissues in zebrafish development. Their findings, published in Nature Communication, may provide new information on normal head development, as well as congenital craniofacial malformations.

“CNCCs have long fascinated biologists with the incredible diversity of cell types they can generate. By studying this process in genetically treatable zebrafish, we have identified many potential switches that allow CNCCs to form these types of cells. very different cells, ”said Gage Crump. , professor of stem cell biology and regenerative medicine at the Keck School of Medicine at USC.

Led by postdoctoral fellow Peter Fabian and doctoral students Kuo-Chang Tseng, Mathi Thiruppathy and Claire Arata, the team of scientists permanently labeled CNCCs with a red fluorescent protein to track cell types originating from CNCCs throughout. the life of the zebrafish. They then used a powerful type of approach, known as ‘single cell genomics’, to identify the full set of active genes and DNA organization across hundreds of thousands of individual CNCCs. The massive amount of data generated forced scientists to develop a new computational tool to make sense of it.

“We created a type of computer analysis that we called ‘Constellations’ because the final visual result of the technique is reminiscent of star constellations in the sky,” Fabian said. “Unlike astrology, our Constellations algorithm can really predict the future of cells and reveal the key genes that probably control their development.”

Thanks to this new bioinformatics approach, the team discovered that CNCCs do not start with all the information necessary to render the immense diversity of cell types. Instead, it is only after dispersing throughout the embryo that CNCCs begin to rearrange their genetic material to become specific tissues. The constellations have precisely identified the genetic signs that point to these specific destinies for CNCCs. Actual experiments confirmed that Constellations had correctly identified the role of a family of “FOX” genes in the formation of facial cartilage and a previously unrecognized function of the “GATA” genes in the formation of the types of gill respiratory cells that fish to breathe.

“By conducting one of the most comprehensive single-cell studies of a vertebrate cell population to date, we not only gained important information about vertebrate head development, but we also created a computational tool. Widely useful for studying the development and regeneration of organ systems throughout the body, ”said Crump.

Additional Crump Lab co-authors included doctoral student Hung-Jhen Chen, postdoctoral fellow Joanna Smeeton, and research technician Nellie Nelson. Smeeton is now an assistant professor at Columbia University and Nelson is a doctoral student at the University of California, Irvine.

The research was funded by the federal National Institutes of Health (grants NIDCR R35 DE027550, NIDCR K99 DE029858, NIDCR F31 DE029682-02, NICHD T32 HD060549).

Source of the story:

Materials provided by USC Keck School of Medicine. Original written by Cristy Lytal. Note: Content can be changed for style and length.

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