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Researchers uncover surprising role of opioid receptors in gut development

Researchers uncover surprising role of opioid receptors in gut development
Rodrigo Moreno Campos is lead researcher and a postdoctoral fellow. Credit: Gustavo Raskosky/Rice University

Researchers at Rice University have revealed a previously unknown function of opioid receptors in the development of the enteric nervous system (ENS), often referred to as the "brain in the gut." This discovery challenges conventional understanding of opioid receptors, shedding new light on their significance beyond pain management and addiction.

Led by Rosa Uribe, an assistant professor of biosciences at Rice and a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar, the research team identified the genes critical for ENS by conducting a series of experiments using zebrafish embryos, which share many genetic similarities with humans. The ENS is a network of neurons in the that plays a vital role in regulating digestive processes.

The team's research was published in PLOS ONE on May 29.

"We found that the opioid signaling pathway is required for the developmental formation of nerves in the gut, an understudied part of the body called the enteric nervous system," Uribe said.

Using gene-editing techniques, the researchers selectively removed (knocked out) a from an entire population of to observe how these genetic alterations affected the formation of gut nerves. This process revealed novel genes, including those encoding opioid receptors, implicated in ENS development.

Contrary to previous assumptions, the researchers found that are not solely involved in pain perception and addiction but are also integral to the developmental formation of gut nerves.

Researchers uncover surprising role of opioid receptors in gut development
Construction of an F0 CRISPR screen for ENS development. (A) tSNE plot shows five distinct sub-clusters after the subset analysis and re-clustering of Clusters 5 and 12 from the [20] 68–70 hpf data set. (B) Violin plots reveal high single-cell expression distribution in sub-cluster 3 of ENS candidate genes. (C) Twelve genes underwent a comprehensive CRISPR screen, involving bioinformatic design, and CRISPR-Cas9 mutagenesis in -8.3phox2bb:Kaede zebrafish larvae to visualize enteric cells. The screening strategy included subsequent genotyping validation and high-content phenotyping. Credit: PLOS ONE (2024). DOI: 10.1371/journal.pone.0303914

"When these receptors were deactivated, the migration and maturation of enteric neurons along the gut were disrupted," Uribe said. That disruption indicates the crucial role of opioid signaling pathways in ENS development.

The team's findings open up new avenues for understanding digestive health and disease. Many infants born with missing gut nerves experience difficulties in passing stool, highlighting the potential impact of this research on pediatric medicine. Understanding the role of opioids in gut development may 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 gut development," Uribe said. "This could have for understanding digestive disorders and potentially lead to new therapeutic approaches."

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

"Our finding is incredible and opens up a whole new avenue of enteric neurodevelopmental biology research in the field," Moreno Campos said. "The implications for congenital, neurological and metabolic disease are great."

More information: Rodrigo Moreno-Campos et al, A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in establishment of the enteric nervous system, PLOS ONE (2024). DOI: 10.1371/journal.pone.0303914

Journal information: PLoS ONE
Provided by Rice University
Citation: Researchers uncover surprising role of opioid receptors in gut development (2024, May 29) retrieved 21 June 2024 from
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