A crowning achievement in understanding head development

A picture of an adult zebrafish head with neural crest-derived cells in red. The single-cell sequence used by the Crump lab to understand how the head skeleton is built and repaired has implications for understanding human craniofacial birth defects and improving repair of skeletal tissues. Credit: Peter.

Cranial neural crest cells are more than just a name. Stem cells can form most of the skull and facial skeleton in fish and humans, but they can also form other parts of the body. Scientists from the lab of Gage Crump created a series of atlases to understand the decisions made by the CNCCs in the development of a fish. Their findings may provide new insights into normal head development and birth defects.

Biologists have long been fascinated by the incredible diversity of cell types generated by CNCCs. Gage Crump, professor of stem cell biology and regenerative medicine at the USC's Keck School of Medicine, said that they have identified many of the potential switches that allow the cells to form different cell types.

The team of scientists permanently labeled the cells with a red fluorescent protein to keep track of which cell types came from the cells. The complete set of active genes and the organization of the DNA across hundreds of thousands of individual CNCCs were identified using a powerful type of approach. Scientists had to develop a new tool to make sense of the huge amount of data generated.

The final visual output of the technique is reminiscent of constellations of stars in the sky. The key genes that likely control their development are revealed by our Constellations algorithm, in contrast to astrology.

The team discovered that the information needed to make the huge diversity of cell types is not always available in the beginning. After the embryo is dispersed, the CNCCs begin reorganizing their genetic material in order to become specific tissues. The genetic signs that are identified by the constellations point to the specific destinies of the CNCCs. The role of a family of "FOX" genes in facial cartilage formation and a previously unappreciated function for "GATA" genes in the formation of gill respiratory cell types were confirmed by real-life experiments.

"We gained significant insights into the development of the head and created a broadly useful computational tool for studying the development and regeneration of organ systems throughout the body," said Crump.

The Crump Lab had additional co-authors that included a student and a research technician. Nelson is a student at the University of California, Irvine.

There is more information about the long-term single-cell profiling of cranial neural crest diversification. There is a DOI titled: 10.1038/s41467-021-27594-w.

Nature Communications is a journal.

A crowning achievement in understanding head development was retrieved on January 10, 2022.

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