How to assemble a complete jaw

Date:
March 10, 2023
Source:
Keck School of Medicine of USC
Summary:
The skeleton, tendons, and glands of a functional jaw all derive
from the same population of stem cells, which arise from a cell
population known as neural crest. To discover how these neural
crest-derived cells know to make the right type of cell in the right
location, researchers focused on a particular gene, Nr5a2, that
was active in a region of the face that makes tendons and glands,
but not skeleton. To understand the role of Nr5a2, the scientists
created zebrafish lacking this gene. These mutant zebrafish
generated excess cartilage and were missing tendons in their jaws.


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FULL STORY ==========================================================================
The skeleton, tendons, and glands of a functional jaw all derive from
the same population of stem cells, which arise from a cell population
known as neural crest. To discover how these neural crest-derived cells
know to make the right type of cell in the right location, researchers
focused on a particular gene, Nr5a2, that was active in a region of the
face that makes tendons and glands, but not skeleton. To understand the
role of Nr5a2, the scientists created zebrafish lacking this gene. These
mutant zebrafish generated excess cartilage and were missing tendons in
their jaws. The scientists then examined the structure of the genome in zebrafish lacking Nr5a2. They found that Nr5a2 was essential for opening
up regions of the genome that enable neural crest cells to maintain their
stem cell features, while at the same time priming these cells to form
tendons and salivary glands later in jaw development.


==========================================================================
A USC-led team of scientists has made a drool-worthy discovery about
how tendons and salivary glands develop in the jaw. Their results are
published in a new study in Developmental Cell.

In order for our jaws to function, they require not only a precisely
patterned skeleton, but also tendons that connect the jaw skeleton
to muscles and salivary glands that lubricate the mouth. Remarkably,
the skeleton, tendons, and glands all derive from the same population of
stem cells, which arise from a cell population known as neural crest. How
these neural crest-derived cells know to make the right type of cell in
the right location has remained a mystery.

To begin answering this question, first author Hung-Jhen (Olivia)
Chen from the lab of corresponding author Gage Crump, professor and
vice-chair of stem cell biology and regenerative medicine at the Keck
School of Medicine of USC, and colleagues examined all the genes that
were active in the developing face of zebrafish. They then honed in on
one particular gene, Nr5a2, that was active in a region of the face that
makes tendons and glands, but not skeleton.

To understand the role of Nr5a2, the scientists created zebrafish lacking
this gene. These mutant zebrafish generated excess cartilage and were
missing tendons in their jaws.

The scientists also developed mice lacking this gene specifically in their neural crest cells. These mice not only had skeletal and tendon defects in their jaws, but also failed to develop salivary glands. Similar defects
were also seen in the middle ear, reflecting a dramatic evolutionary
transition in which part of the fish jaw became the mammalian middle ear.

To clarify how this was happening, the scientists examined the structure
of the genome in zebrafish lacking Nr5a2. They found that Nr5a2 was
essential for opening up regions of the genome that enable neural crest
cells to maintain their stem cell features, while at the same time priming these cells to form tendons and salivary glands later in jaw development.

"Discovery of a very specific role of Nr5a2 in jaw patterning was
unexpected, as this gene had previously been shown to be essential for maintaining embryonic stem cells," said Crump. "Our work shows how a key
stem cell factor can be used in a different way later in development to
control how diverse cell types are made." Additional co-authors include Lindsey Barske, who completed her postdoctoral training at USC and is
now a faculty member at Cincinnati Children's Hospital Medical Center;
Jared Talbot from the University of Maine; Olivia Dinwoodie and Abigail
Tucker from King's College London; Ryan Roberts, Christian Jimenez, and
Amy Merrill from USC; and D'Juan Farmer who completed his postdoctoral
training at USC and is now a faculty member at UCLA.

Funding for this research was provided by the National Institute of Dental Craniofacial Research (grants R21DE029656 and R35DE027550), the Howard
Hughes Medical Institute's Hannah H. Gray Fellows Program, and the King's College London Medical Research Council Doctoral Training Partnership.

* RELATED_TOPICS
o Health_&_Medicine
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# Developmental_Biology # Biotechnology #
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* RELATED_TERMS
o Human_skeleton o Gene_therapy o Stem_cell o Embryo o
Adult_stem_cell o Stem_cell_treatments o Tendon o Somatic_cell

========================================================================== 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. Hung-Jhen Chen, Lindsey Barske, Jared C. Talbot, Olivia
M. Dinwoodie,
Ryan R. Roberts, D'Juan T. Farmer, Christian Jimenez, Amy
E. Merrill, Abigail S. Tucker, J. Gage Crump. Nuclear receptor Nr5a2
promotes diverse connective tissue fates in the jaw. Developmental
Cell, 2023; DOI: 10.1016/j.devcel.2023.02.011 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/03/230310123924.htm

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