Unravelling the origins of the human spine

Date:
April 28, 2022
Source:
European Molecular Biology Laboratory
Summary:
Scientists have recapitulated in the laboratory how the
cellular structures that give rise to our spinal column form
sequentially. They have created a 3D in vitro model that mimics
how the precursor structures that give rise to the spinal column
form during human embryonic development.



FULL STORY ==========================================================================
The spinal column is the central supporting structure of the skeleton
in all vertebrates. Not only does it provide a place for muscles to
attach, it also protects the spinal cord and nerve roots. Defects in its development are known to cause rare hereditary diseases. Researchers from
the Ebisuya Group at EMBL Barcelona have now created a 3D in vitromodel
that mimics how the precursor structures that give rise to the spinal
column form during human embryonic development.


==========================================================================
The spinal column consists of 33 vertebrae, which form pairs of precursor structures called somites. Somites give rise to not only our vertebrae,
but also our ribs and skeletal muscles. To ensure that these structures
are formed correctly, somite development is tightly regulated, and
each pair of somites arises at a particular sequential time point in development. This process is controlled by the segmentation clock,
which is a group of genes that creates oscillatory waves, every wave
giving rise to a new pair of somites.

"For the first time, we have been able to create periodic pairs of
human mature somites linked to the segmentation clock in the lab," said
Marina Sanaki- Matsumiya, first author of the study published in Nature Communications. Using this approach, the researchers developed a 3D in vitromodel of human somite formation, also known as 'somitogenesis'.

Creating a robust somitogenesis process The team cultured human induced pluripotent stem cells (hiPSC) in the presence of a cocktail of signalling molecules that induce cell differentiation. Three days later, the cells
started to elongate and create anterior (top) and posterior (bottom)
axes. At that point, the scientists added Matrigel to the culture
mix. Matrigel is what some scientists call the magic powder: a protein
mixture that is critical to many developmental processes. This process eventually led to the formation of somitoids -- in vitroequivalents of
human somite precursor structures.

To test whether the segmentation clock regulates somitogenesis in these somitoids, the researchers monitored the expression patterns of HES7,
the core gene involved in the process. They found clear evidence of oscillations, especially when somitogenesis was about to start. The
somites that formed also had clear markers of epithelization -- an
important step in their maturation.

Somite size matters The Ebisuya group studies how and why we humans are different from other species when it comes to embryonic development. One
of the model systems they use to understand interspecies differences
is the segmentation clock. In 2020, the group uncovered that the
oscillation period of the human segmentation clock is longer than the
mouse segmentation clock.

The current study also shows a link between the size of somites
and the segmentation clock. "The somites that were generated had a
constant size, independently of the number of cells used for the initial somitoid. The somite size did not increase even if the initial cell number did." explained Sanaki- Matsumiya. "This suggests that the somites have
a preferred species-specific size, which might be determined by local
cell-cell interactions, the segmentation clock, or other mechanisms."
To study this further, Miki Ebisuya and her group are now planning to
grow somitoids of different species and compare them. The researchers
are already working on several mammalian species, including rabbits,
cattle, and rhinoceroses, setting up a 'stem cell zoo' in the lab.

"Our next project will focus on creating somitoids from different species, measure their cell proliferation and cell migration speed to establish
what and how somitogenesis is different among species," said Ebisuya.


========================================================================== Story Source: Materials provided by
European_Molecular_Biology_Laboratory. Original written by Carla
Manzanas. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Marina Sanaki-Matsumiya, Mitsuhiro Matsuda, Nicola Gritti,
Fumio Nakaki,
James Sharpe, Vikas Trivedi, Miki Ebisuya. Periodic formation
of epithelial somites from human pluripotent stem cells. Nature
Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29967-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220428085852.htm

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