Neural disruptions underlying feeding, swallowing disorders in children identified
Neuroscience team provides insight on early cellular interactions
underlying cranial nerve development
Date:
February 23, 2022
Source:
Virginia Tech
Summary:
Scientists depict the early development of pain-sensing and
movement- sensing neurons in the face and throat. The findings
reveal a previously unexplored feature of brain and cranial nerve
development underlying eating, swallowing, and speech.
FULL STORY ========================================================================== Every time you chew, talk, yawn, or sense the zap of a toothache, cranial
nerve cells are shuttling electrochemical signals to your brain. Some
of these neurons detect pain, while others sense facial muscle movements
or sensations in the skin.
==========================================================================
Now, in a new study published in Disease Models & Mechanisms, Fralin
Biomedical Research Institute at VTC scientists led by Anthony-Samuel
LaMantia depict the early development of pain-sensing and movement-sensing neurons in the face and throat. The findings reveal a previously
unexplored feature of brain and cranial nerve development underlying
eating, swallowing, and speech.
"We were able to show for the first time that this momentary interaction between two groups of cells plays a crucial role in regulating movement
and pain-sensing innervation in the face," LaMantia, professor and
director of the Fralin Biomedical Research Institute's Center for
Neurobiology Research.
The researchers examined early neural development in mice embryos with
DiGeorge syndrome, a rare genetic disorder associated with neural and
facial abnormalities. Like human patients born with DiGeorge, mice can
carry the identical genetic mutation, providing an ideal model to study
where development goes awry at the cellular and molecular level.
Children born with DiGeorge commonly have trouble coordinating suckling
and swallowing milk, a condition called pediatric dysphagia, but it's
unclear how the mutation causes these functional abnormalities. While
mouth, tongue, and throat movements involved in eating are controlled
by motor neurons, mechanosensory neurons -- a subject of this study --
detect and integrate movement signals to fine-tune the behavior. The
study also evaluated pain- sensing neurons, or nociceptors, which monitor potentially harmful aspects of eating behavior, including excessive temperatures and irritants like capsaicin in hot peppers.
LaMantia and his laboratory have been studying this syndrome to
disentangle facets of cranial nerve development and oropharyngeal
behaviors for a decade.
========================================================================== Based on their prior research, the scientists knew that on day nine of
mouse embryo development, two groups of cells -- neural crest and placode
cells - - needed to meet to begin blueprinting the facial nerve. They
knew that in the syndromic mice, something went wrong at this stage of development that had deleterious behavioral consequences, but it needed
further investigation.
"Starting out, we weren't sure if these two groups of cells just weren't migrating together to meet in the proper place, or if they were in the
right place at the right time, and just failed to communicate," LaMantia
said. With this newly published data, LaMantia's lab now suspects the
latter is true.
Combining in vivo analysis and imaging to visualize a variety of molecular markers, the researchers found that neural crest cells were turning
into pain- sensing neurons far too soon. This premature differentiation
caused the quantity of placode cells, which become mechanosensory neurons,
to increase relative to neural crest cells.
This study builds on previous work by LaMantia's lab. Seven years ago, the researchers examined if the developing cranial nerve neurons were growing
axons that met functional targets in the face, mouth, and throat. They
found that compared with ordinary mice, the syndromic mice embryos lacked proper innervation -- the axons were shorter, misplaced, and disorganized.
"Not only were the neurons confused about what they were supposed to do,
their axons also didn't have precise destinations -- they just got lost," LaMantia said.
In a follow-up study, LaMantia's lab identified key genes involved in regulating normal axonal growth in the cranial nerve. Remarkably, the researchers were able to restore ordinary cranial nerve growth in mice
with DiGeorge syndrome by suppressing a specific gene.
The new discovery reveals how changes in gene expression associated with DiGeorge syndrome destabilize sensory neuron growth by interrupting a
key interaction between neural crest and placode cells. LaMantia's lab
now aims to uncover the molecular signals that these cell groups need
to assemble a healthy cranial nerve.
"Now that we've identified the point of divergence where these functional oropharyngeal problems originate, our next step will be to understand the vocabulary these cells use to communicate with each other," LaMantia said.
This research was funded in part by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, part of the
National Institutes of Health; and the Fralin Biomedical Research
Institute. LaMantia is also a professor in the College of Science
Department of Biological Sciences and in the Virginia Tech Carilion
School of Medicine Department of Pediatrics.
special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by Virginia_Tech. Original written by
Whitney Slightham.
Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Beverly A. Karpinski, Thomas M. Maynard, Corey A. Bryan, Gelila
Yitsege,
Anelia Horvath, Norman H. Lee, Sally A. Moody, Anthony-Samuel
LaMantia.
Selective disruption of trigeminal sensory neurogenesis
and differentiation in a mouse model of 22q11.2 deletion
syndrome. Disease Models & Mechanisms, 2022; 15 (2) DOI:
10.1242/dmm.047357 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/02/220223085804.htm
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