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Opioid Receptors Key to Gut Nervous System Development

Summary: Researchers have discovered a new role for opioid receptors in the development of the enteric nervous system (ENS), the “brain in the gut.” This discovery challenges the conventional understanding of opioid receptors, highlighting their importance beyond pain management and addiction.

The study used zebrafish embryos to reveal that opioid receptors are essential for the formation of intestinal nerves, which could impact treatments for congenital digestive disorders.

Highlights:

  • Opioid receptors are essential for the development of the enteric nervous system.
  • Disruption of these receptors affects the migration and maturation of intestinal neurons.
  • The findings could lead to new treatments for congenital digestive disorders.

Source: Rice University

Rice University researchers have revealed a previously unknown function of opioid receptors in the development of the enteric nervous system (ENS), often referred to as “brain in the gut.”

This discovery challenges the conventional understanding of opioid receptors, shedding new light on their importance beyond pain management and addiction.

Led by Rosa Uribe, assistant professor of biosciences at Rice and Cancer Prevention and Research Institute of Texas (CPRIT) fellow, the research team identified genes essential for ENS development by conducting a series of experiments using zebrafish embryos, which share many genes. similarities with humans.

Understanding the role of opioids in intestinal development could pave the way for innovative treatments for congenital digestive disorders. Credit: Neuroscience News

The ENS is a neural network in the gastrointestinal tract that plays an essential role in regulating digestive processes.

The team’s research was published in the PLOS ONE newspaper on May 29.

“We discovered that the opioid signaling pathway is necessary for the developmental formation of nerves in the gut, a little-studied part of the body called the enteric nervous system,” Uribe said.

Using gene editing techniques, researchers selected or knocked out a single gene from an entire population of zebrafish embryos to observe how these genetic alterations affected intestinal nerve formation. This process revealed new genes, notably those encoding opioid receptors, involved in the development of ENS.

Contrary to previous hypotheses, researchers discovered that opioid receptors are not only involved in pain perception and addiction, but are also an integral part of the developmental formation of intestinal nerves.

“When these receptors were deactivated, the migration and maturation of enteric neurons along the intestine was disrupted,” Uribe said. This disruption indicates the crucial role of opioid signaling pathways in the development of ENS.

The team’s findings open new avenues for understanding digestive health and diseases. Many infants born with missing intestinal nerves experience difficulty passing stools, highlighting the potential impact of this research on pediatric medicine. Understanding the role of opioids in intestinal development could pave the way for innovative treatments for congenital digestive disorders.

“Our research unveils a new aspect of opioid receptor function and highlights their unexpected role in intestinal development,” Uribe said. “This could have profound implications in understanding digestive disorders and potentially lead to new therapeutic approaches.” »

Additionally, the study identified other genes, such as VGF, with implications for gastrointestinal health. Further research in this area could provide insight into the complex interplay between genes, the nervous system and digestive function, said lead researcher and postdoctoral researcher Rodrigo Moreno Campos.

“Our discovery is incredible and opens a whole new avenue of enteric neurodevelopmental biology research in this area,” said Moreno Campos. “The implications for congenital, neurological and metabolic diseases are significant. »

Uribe joined Rice in 2017 as a CPRIT fellow. She received a bachelor’s degree in cellular and molecular biology from San Francisco State University in 2006 and a doctorate in molecular cellular and developmental biology from the University of Texas at Austin in 2012. In 2020, she won a NSF CAREER Award.

Funding: This study was supported by National Institutes of Health Grant R01DK124804 to RAU and by National Science Foundation Grant 1942019 to RAU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

About this neuroscience research news

Author: Marcy de Luna
Source: Rice University
Contact: Marcy de Luna – Rice University
Picture: Image is credited to Neuroscience News

Original research: Free access.
“A targeted CRISPR-Cas9-mediated F0 screen identifies genes involved in the establishment of the enteric nervous system” by Rosa Uribe et al. PLOS ONE


Abstract

A targeted CRISPR-Cas9-mediated F0 screen identifies genes involved in enteric nervous system establishment

The vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glial cells residing throughout the gastrointestinal (GI) tract. Overseeing essential gastrointestinal functions such as gut motility and fluid balance, the ENS serves as an essential bidirectional link in the gut-brain axis. Early in development, the ENS derives primarily from enteric neural crest cells (ENCC).

Disturbances in ENCC development, such as in conditions such as Hirschsprung’s disease (HSCR), lead to the absence of ENCC in the digestive tract, particularly in the colon. In this study, using zebrafish, we designed a in vivo CRISPR-based F0 screen using a robust and rapid pipeline integrating single-cell RNA sequencing, CRISPR reverse genetics and high-content imaging.

Our results reveal diverse genes, including those encoding opioid receptors, as possible regulators of ENS establishment. Furthermore, we present evidence suggesting the involvement of opioid receptors in the neurochemical coding of the larval ENS.

In summary, our work presents a novel, efficient CRISPR screen targeting ENS development, facilitating the discovery of previously unknown genes and increasing knowledge about nervous system construction.

News Source : neurosciencenews.com
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