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.
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
Cell Biology
Kathy Nga-Chu Lui, Elly Sau-Wai Ngan
Summary: Hirschsprung disease is a complex congenital disorder caused by defects in the development of the enteric nervous system. The use of human induced pluripotent stem cells has provided new tools for understanding the disease and developing therapies. These stem cell-based models complement traditional genetic screens and bioinformatic approaches, and have potential applications in translational medicine and drug discovery.
Article
Oncology
Leticia Villalba-Benito, Daniel Lopez-Lopez, Ana Torroglosa, Carlos S. Casimiro-Soriguer, Berta Luzon-Toro, Raquel Maria Fernandez, Maria Jose Moya-Jimenez, Guillermo Antinolo, Joaquin Dopazo, Salud Borrego
Summary: This study reveals a decrease in global DNA methylation in HSCR patients in CpG context, along with a greater hypomethylation of DMRs. The downregulation of Methyltransferase 3b in EPCs from HSCR patients correlates with these findings. New potential susceptibility genes for HSCR have been identified through the comparative analysis of DMRs, highlighting the importance of an adequate methylation pattern for proper ENS development.
CLINICAL EPIGENETICS
(2021)
Article
Environmental Sciences
Jing Wang, Xinyao Meng, Chenzhao Feng, Jun Xiao, Xiang Zhao, Bo Xiong, Jiexiong Feng
Summary: Hirschsprung disease (HSCR) is a congenital disease characterized by a deficiency of enteric neurons, with genetic and environmental factors playing a role. Research suggests that the UV filter component BP-3 may inhibit the development of the enteric nervous system (ENS) through modulation of the MAPK/ERK signaling pathway. These findings provide insights into potential mechanisms for HSCR development and suggest therapeutic targets for intervention.
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
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
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)
Article
Cell Biology
Yan-Jiao Lu, Wen-Wen Yu, Meng-Meng Cui, Xian-Xian Yu, Huan-Lei Song, Mei-Rong Bai, Wen-Jie Wu, Bei-Lin Gu, Jun Wang, Wei Cai, Xun Chu
Summary: Common variants of DSCAM were associated with HSCR risk in the Han Chinese population, while common variants of BACE2 were not. Knockdown of both dscams and bace2 in zebrafish resulted in reduced enteric neurons in the hindgut, while overexpression of DSCAM and BACE2 did not affect neuron number in zebrafish hindgut.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Amy Marie Holland, Ana Carina Bon-Frauches, Daniel Keszthelyi, Veerle Melotte, Werend Boesmans
Summary: The enteric nervous system (ENS) plays a crucial role in regulating gastrointestinal function, and its dysfunction is closely linked to gastrointestinal diseases. Recent research indicates that the multifaceted connections between the ENS, intestinal epithelium, immune system, and gut microbiome are essential for maintaining gastrointestinal homeostasis. Therefore, the ENS plays a significant role in the pathogenesis of enteric neuropathies, inflammatory bowel diseases, and colorectal cancer.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Multidisciplinary Sciences
R. Diposarosa, N. A. Bustam, Edhyana Sahiratmadja, P. S. Susanto, Y. Sribudiani
Summary: Hirschsprung's disease is a developmental disorder of the enteric nervous system derived from neural crest cells, and changes in gene expression may contribute to its pathogenesis. Deviant genetic and epigenetic patterns, such as DNA methylation, histone modification, and miRNA regulation, can play a role in the development of neurocristopathy. Specifically, epigenetic regulation of miRNA expression and its relationship to cellular interactions and gene activation through major pathways are discussed in the context of Hirschsprung's disease.
Article
Genetics & Heredity
Sumantra Chatterjee, Lauren E. Fries, Or Yaacov, Nan Hu, Hanna E. Berk-Rauch, Aravinda Chakravarti
Summary: Hirschsprung disease is associated with deficiency of the RET receptor tyrosine kinase, resulting in loss of cells of the enteric nervous system during fetal gut development. This study demonstrates that variants in RET enhancers specifically alter the human fetal gut development program by decreasing gene expression of RET and other genes involved in Hirschsprung disease, leading to differential expression of genes across neuronal and mesenchymal functions. The findings suggest that genes reducing RET proliferative activity can potentially cause Hirschsprung disease.
Article
Pediatrics
Jing Wang, Jun Xiao, Xinyao Meng, Xufeng Chu, Di Di Zhuansun, Bo Xiong, Jiexiong Feng
Summary: The study revealed that the expression of NOX5 is significantly decreased in the aganglionic segment of HSCR colon patients. In zebrafish, NOX5 expression seems to be enriched in the nervous system. However, knockdown of NOX5 did not affect the development of the enteric nervous system and gastrointestinal motility in zebrafish.
Article
Genetics & Heredity
Keqiang Liu, Ru Chen, Minzhong Zhang, Yiming Gong, Yong Wang, Wei Cai
Summary: Variants in the ERBB3 gene can lead to different disease phenotypes, including lethal congenital contracture syndrome and evident intestinal dysmotility. These findings help to better characterize the ERBB3-related phenotype spectrum, and reveal phenotypic variability caused by ERBB3 deficiency among different individuals.
Review
Pediatrics
Weikang Pan, Allan M. Goldstein, Ryo Hotta
Summary: Despite significant progress in understanding the causes and mechanisms of Hirschsprung disease (HSCR), it is still challenging to diagnose and manage the condition accurately in its early stages. Long-term complications following surgery for HSCR, such as fecal incontinence, constipation, and Hirschsprung-associated enterocolitis (HAEC), remain problematic. However, recent research advancements, including advanced imaging techniques and the use of neuronal stem cells, offer new possibilities for the diagnosis and treatment of HSCR.
JOURNAL OF PEDIATRIC SURGERY
(2022)