Review
Cell Biology
Werend Boesmans, Amelia Nash, Kinga R. Tasnady, Wendy Yang, Lincon A. Stamp, Marlene M. Hao
Summary: Enteric glia are support cells of the enteric nervous system that play a vital role in regulating gut functions and maintaining homeostasis. Their plasticity and heterogeneity make them neural precursors with the potential for neurogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell & Tissue Engineering
Rhian Stavely, Sukhada Bhave, Wing Lam N. Ho, Minhal Ahmed, Weikang Pan, Ahmed A. Rahman, Jessica Ulloa, Nicole Bousquet, Meredith Omer, Richard Guyer, Nandor Nagy, Allan M. Goldstein, Ryo Hotta
Summary: The interaction between ENSCs and EMCs plays a crucial role in the normal development of the enteric nervous system, with potential implications for treating Hirschsprung disease. EMCs enhance the expansion and neurosphere-forming ability of ENCDCs through paracrine factors, leading to functional neurons and successful transplantation in the HSCR model.
Review
Biochemistry & Molecular Biology
Zhixin Li, Elly Sau-Wai Ngan
Summary: With the rapid development of single-cell sequencing technologies, the use of single-cell multimodal sequencing has become a powerful strategy in discovering rare cells and understanding biological processes. This article summarizes recent findings in single-cell multimodal sequencing, particularly focusing on single-cell RNA sequencing (scRNA-seq) in the enteric nervous system (ENS). The studies have revealed the heterogeneity of ENS cells at different developmental stages and identified novel cell types. The application of single-cell multimodal omics techniques in profiling disease mechanisms and cellular drug responses is expected to revolutionize biomedical research.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Neurosciences
Dipa Natarajan, Conor McCann, Justine Dattani, Vassilis Pachnis, Nikhil Thapar
Summary: The majority of the enteric nervous system is formed by vagal neural crest cells. Hirschsprung disease is characterized by absence of enteric ganglia from the distal colon. Mutations in the RET receptor tyrosine kinase have been identified in familial cases of Hirschsprung disease. This study demonstrates that normal RET receptor activity is required for migration of enteric nervous system progenitors throughout the gut. Failure of colonisation of the distal intestine and deficits in neuronal circuitry contribute to the pathogenesis of Hirschsprung disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Developmental Biology
Rhian Stavely, Ryo Hotta, Richard A. Guyer, Nicole Picard, Ahmed A. Rahman, Meredith Omer, Adam Soos, Emoke Szocs, Jessica Mueller, Allan M. Goldstein, Nandor Nagy
Summary: The development of the enteric nervous system is dependent on the colonization of the intestine by enteric neural crest-derived cells (ENCDCs). ENCDCs at the wavefront, which are highly migratory and proliferative, exhibit distinct molecular characteristics compared to trailing ENCDCs. These wavefront ENCDCs show altered expression of genes associated with migration and lack expression of genes related to neuronal or glial maturation.
Review
Biochemistry & Molecular Biology
Richard A. Guyer, Jessica L. Mueller, Allan M. Goldstein
Summary: With the advancement of technology, single-cell sequencing has become a common tool to analyze cellular diversity and reveal cellular diversity within organs. The application of these methods in the study of the enteric nervous system has provided abundant data and biological insights. As technology continues to evolve, these methods may become commonplace in enteric nervous system research and diagnostic testing.
Article
Developmental Biology
Nandor Nagy, Tamas Kovacs, Rhian Stavely, Viktoria Halasy, Adam Soos, Emoke Szocs, Ryo Hotta, Hannah Graham, Allan M. Goldstein
Summary: The migration and proliferation of ENCCs are crucial for ENS formation, with the ceca playing an important role in ENS development. The non-canonical Wnt signaling pathway regulates ENCC differentiation by inhibiting enteric neuronal differentiation.
Article
Cell Biology
Yuuki Shikaya, Yuta Takase, Ryosuke Tadokoro, Ryo Nakamura, Masafumi Inaba, Yoshiko Takahashi
Summary: Gut peristaltic movements are crucial for effective transportation and digestion/absorption of ingested materials. The cellular functions underlying these movements along the gut axis during development are largely unexplored. By studying chicken embryonic gut, we found that peristaltic movements start from the posterior duodenum and become confined to specific regions during development. Manipulations of the enteric nervous system disrupted the distribution patterns of peristaltic waves and affected the transportation of ingested material. We also discovered a functional coupling between the hindgut and cloaca.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Helen Rueckert, Julia Ganz
Summary: The enteric nervous system (ENS) is crucial for gastrointestinal functions, and understanding the regulatory mechanisms of regeneration is essential for treating ENS disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Tamas Kovacs, Viktoria Halasy, Csongor Petho, Emoke Szocs, Adam Soos, David Dora, Pascal de Santa Barbara, Sandrine Faure, Rhian Stavely, Allan M. Goldstein, Nandor Nagy, Nicolas Pilon
Summary: The enteric nervous system (ENS) is derived from vagal neural crest cells and plays a crucial role in gastrointestinal development. This study shows that the avian ceca, located at the junction of the midgut and hindgut, are necessary for hindgut ENS development. It also highlights the importance of bone morphogenetic protein-4 (BMP4) and glial cell line-derived neurotrophic factor (GDNF) signaling pathways in the migration of enteric neural crest-derived cells (ENCDC) and the formation of enteric ganglia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yue Ji, Paul Kwong-Hang Tam, Clara Sze-Man Tang
Summary: The development of the enteric nervous system relies on the interaction between enteric neural crest cells and the neural stem cell niche. Defects in ENCCs may lead to ENS dysfunction. HSCR patients may have niche defects affecting ECM-cell interaction, suggesting the need for complementary therapies involving drugs and niche-based treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Developmental Biology
Viktoria Halasy, Emoke Szocs, Adam Soos, Tamas Kovacs, Nora Pecsenye-Fejszak, Ryo Hotta, Allan M. Goldstein, Nandor Nagy
Summary: The enteric nervous system (ENS) and peripheral ganglia provide innervation to the gastrointestinal tract, but the molecular mechanisms controlling extrinsic nerve fiber growth are not well understood. This study investigates the role of CXCR4 and CXCL12 in the development of colorectal innervation. It is found that CXCR4 is expressed in nerve fibers arising from the nerve of Remak (NoR) and the pelvic plexus, while CXCL12 is localized to the hindgut and enteric ganglia. Overexpression of CXCL12 enhances axonal projections to the gut from the NoR, while CXCR4 inhibition disrupts nerve fiber extension.
Article
Cell Biology
Aubrey G. A. Howard, Aaron C. Nguyen, Joshua Tworig, Priya Ravisankar, Eileen W. Singleton, Can Li, Grayson Kotzur, Joshua S. Waxman, Rosa A. Uribe
Summary: Neural crest cells (NCCs) are migratory and multipotent stem cells essential to vertebrate embryonic development. This study identifies the gene Hoxb5b as a regulator of NCC development, demonstrating that elevated Hoxb5b levels promote expansion of zebrafish NCCs and specifically expand expression domains of vagal NCC markers. The study also shows that early increase in vagal NCCs leads to supernumerary enteric neural progenitors, but these fail to properly expand into enterically fated neurons in the gut tissue.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Genetics & Heredity
Wendy Yang, Szu-Chieh Chen, Tse-En Wang, Pei-Shiue Tsai, Jeng-Chang Chen, Pei-Lung Chen
Summary: A study identified an L1CAM gene variation associated with mild hydrocephalus and HSCR, and introduced a similar variation into mice using the CRISPR-EZ method. Different phenotypes were observed in the mice, with no prominent hydrocephalus or HSCR-like symptoms, but male infertility was noticed after three generations. Shorter L1cam isoform proteins were found to be overexpressed in the intestine of L1cam knockdown mice, indicating their potential role in protecting against HSCR.
Article
Pharmacology & Pharmacy
Masato Maruyama, Minami Yoshikata, Mana Sakaguchi, Shizuka Wakushima, Kazutaka Higaki
Summary: The role of the enteric nervous system (ENS) in drug absorption is not well understood. In this study, a co-culture system of Caco-2 cells and enteric neurons was established to investigate the effect of ENS on drug transport across intestinal epithelial cells. The co-culture was found to enhance the transport of fluorescein isothiocyanate-labeled dextran-4 via the paracellular route, suggesting that enteric neurons can facilitate drug transport by opening tight junctions. However, no changes in the permeability of antipyrine were observed, indicating that enteric neurons do not affect passive transport via the transcellular pathway.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
