A crowning achievement in understanding head development

Date:
January 10, 2022
Source:
Keck School of Medicine of USC
Summary:
To understand how cranial neural crest cells (CNCCs) help form
many more body parts than the skull and facial skeleton, scientists
from the lab of Gage Crump created a series of atlases over time to
understand the molecular decisions by which CNCCs commit to forming
specific tissues in developing zebrafish. The researchers labeled
and tracked CNCCs throughout the lifetime of zebrafish. With the
help of a new computational analysis they created, they identified
genetic signs that point to the specific tissues CNCCs were destined
to form. The researchers also identified many of the potential
switches that allow CNCCs to form these very different cell types.



FULL STORY ========================================================================== Cranial neural crest cells, or CNCCs, contribute to many more body parts
than their humble name suggests. These remarkable stem cells not only
form most of the skull and facial skeleton in all vertebrates ranging
from fish to humans, but also can generate everything from gills to
the cornea. To understand this versatility, scientists from the lab
of Gage Crump created a series of atlases over time to understand
the molecular decisions by which CNCCs commit to forming specific
tissues in developing zebrafish. Their findings, published in Nature Communications, may provide new insights into normal head development,
as well as craniofacial birth defects.


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

Led by postdoc Peter Fabian and PhD students Kuo-Chang Tseng, Mathi
Thiruppathy and Claire Arata, the team of scientists permanently labeled
CNCCs with a red fluorescent protein to keep track of which cell types
came from CNCCs throughout the lifetime of zebrafish. They then used a
powerful type of approach, known as "single-cell genomics," to identify
the complete set of active genes and the organization of the DNA across hundreds of thousands of individual CNCCs. The massive quantity of data generated required the scientists to develop a new computational tool
to make sense of it.

"We created a type of computational analysis that we called
'Constellations,' because the final visual output of the technique is reminiscent of constellations of stars in the sky," said Fabian. "In
contrast to astrology, our Constellations algorithm really can predict
the future of cells and reveal the key genes that likely control
their development." Through this new bioinformatic approach, the team discovered that CNCCs do not start out with all the information required
to make the huge diversity of cell types. Instead, only after they
disperse throughout the embryo do CNCCs begin reorganizing their genetic material in preparation for becoming specific tissues. Constellations accurately identified genetic signs that point to these specific destinies
for CNCCs. Real-life experiments confirmed that Constellations correctly pinpointed 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 that allow fish to breathe.

"By conducting one of the most comprehensive single-cell studies of
a vertebrate cell population to date, we not only gained significant
insights into the development of the vertebrate head, but also created
a broadly useful computational tool for studying the development and regeneration of organ systems throughout the body," said Crump.

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

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

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dreams in this free online course from New Scientist -- Sign_up_now_>>> academy.newscientist.com/courses/science-of-sleep-and-dreams ========================================================================== Story Source: Materials provided by
Keck_School_of_Medicine_of_USC. Original written by Cristy Lytal. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Peter Fabian, Kuo-Chang Tseng, Mathi Thiruppathy, Claire Arata,
Hung-Jhen
Chen, Joanna Smeeton, Nellie Nelson, J. Gage Crump. Lifelong
single-cell profiling of cranial neural crest diversification
in zebrafish. Nature Communications, 2022; 13 (1) DOI:
10.1038/s41467-021-27594-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220110103248.htm
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