How bone-bordering cells may help shape a skull

Date:
December 9, 2021
Source:
The Mount Sinai Hospital / Mount Sinai School of Medicine
Summary:
In a study of mice, scientists showed how the activity of one gene,
turned on in a newly discovered group of bone-bordering cells,
may play an important role in shaping the skull. The skulls of
mice that were missing the gene were misshapen and were depleted
of the cells in a manner that is reminiscent of craniosynostosis,
a developmental disorder that affects about one out every 2,500
babies born in the United States.



FULL STORY ==========================================================================
A skull is not one single bone but rather a collection of bone plates
joined together early in development. In a study of mice, scientists at
the Icahn School of Medicine at Mount Sinai showed how the activity of
one gene, turned on in a newly discovered group of bone-bordering cells,
may play an important role in shaping the skull. The skulls of mice that
were missing the gene were misshapen and were depleted of the cells in a
manner that is reminiscent of craniosynostosis, a developmental disorder
that affects about one out every 2,500 babies born in the United States.


==========================================================================
The lead author of the study was Greg Holmes, PhD, Assistant Professor
of Genetics and Genomic Sciences at Icahn Mount Sinai.

The study focused on the cells of the coronal suture, a fibrous joint that connects the front and middle bone plates. In humans, it runs across the
top of the skull, from one temple to the other. Throughout development,
the suture is filled with a buffering tissue called mesenchyme, which
contains stem cells.

The stem cells provide a constant source of new bone cells, or
osteoblasts, which are needed as the plates on either side grow and the
skull expands. In adults, these stem cells are depleted and the joints
between the bone plates fuse.

Craniosynostosis is a birth defect in which this fusion happens
prematurely, resulting in babies born with misshapen skulls who may
develop neurological problems. Scientists have shown that about 25
percent of cases are linked to genetic mutations and that normal suture development is controlled by a variety of growth factors. Of all the
sutures needed to form a skull, the coronal suture is commonly affected
in craniosynostosis.

In this study, the Holmes lab worked with researchers in the labs of
Bin Zhang, PhD, Harm van Bakel, PhD, and Ethylin Wang Jabs, MD, of Icahn
Mount Sinai.

Together they studied how the genetic activity in the cells of the coronal suture changes during early development. To do this, they measured the
RNA levels of individual suture cells from embryonic mice about one to
three days before the mice were normally born.

Their results suggested that a gene encoding a molecule called hedgehog interacting protein (HHIP) plays a unique and critical role in coronal
suture development. The gene was more active in a novel group of
mesenchyme cells than it was in osteoblasts. In fact, the scientists saw
the opposite trend when they looked at the cells of other sutures. Tracing experiments suggested that after birth the coronal suture osteoblasts
were derived from these mesenchyme cells.

Moreover, the skulls of embryonic mutant mice that were missing the HHIP
gene were shaped differently than those from normal mice. Specifically,
there were fewer mesenchymal cells separating the skull bones and the
mutant coronal suture was close to fusing.

Hedgehog proteins are growth factors known to guide normal growth and development in a variety of species, including the promotion of bone
growth.

HHIP is known to inhibit hedgehog activity. To the authors of this study,
their results suggest that the HHIP gene reduced hedgehog activity to
allow normal development of the coronal suture. They hope that advanced single-cell genetic studies like this one will give researchers a
more thorough understanding of how a skull is shaped under healthy and
disease conditions.

========================================================================== Story Source: Materials provided by The_Mount_Sinai_Hospital_/_Mount_Sinai_School_of Medicine. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Greg Holmes, Ana S. Gonzalez-Reiche, Madrikha Saturne, Susan
M. Motch
Perrine, Xianxiao Zhou, Ana C. Borges, Bhavana Shewale, Joan T.

Richtsmeier, Bin Zhang, Harm van Bakel, Ethylin Wang
Jabs. Single-cell analysis identifies a key role for Hhip in murine
coronal suture development. Nature Communications, 2021; 12 (1)
DOI: 10.1038/s41467-021- 27402-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211209123602.htm

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