ArticleGastroenterology2011
Expression level of Hand2 affects specification of enteric neurons and gastrointestinal function in mice.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota.Gut microbes · 2025Article
- Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects.Development (Cambridge, England) · 2025Article
- Differences in enteric neuronal density in the NSE-Noggin mouse model across institutes.Scientific reports · 2024Article
- Effects of the long-term influence of bisphenol A and bisphenol S on the population of nitrergic neurons in the enteric nervous system of the mouse stomach.Scientific reports · 2023Article
- Epigenetic silencing and tumor suppressor gene of HAND2 by targeting ERK signaling in colorectal cancer.Cell communication and signaling : CCS · 2022Article
- Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development.PLoS genetics · 2021Article
- Large intestine embryogenesis: Molecular pathways and related disorders (Review).International journal of molecular medicine · 2020Review
- Dlx1/2 mice have abnormal enteric nervous system function.JCI insight · 2020Article
- Loss of Tbx3 in murine neural crest reduces enteric glia and causes cleft palate, but does not influence heart development or bowel transit.Developmental biology · 2018Article
- Development of the Enteric Nervous System: A Genetic Guide to the Perplexed.Gastroenterology · 2018Article
- Optogenetic and chemogenetic techniques for neurogastroenterology.Nature reviews. Gastroenterology & hepatology · 2018Review
- Regulatory Logic Underlying Diversification of the Neural Crest.Trends in genetics : TIG · 2017Review
- Enteric nervous system development: A crest cell's journey from neural tube to colon.Seminars in cell & developmental biology · 2017Review
- Defining the transcriptomic landscape of the developing enteric nervous system and its cellular environment.BMC genomics · 2017Article
- Advances in understanding functional variations in the Hirschsprung disease spectrum (variant Hirschsprung disease).Pediatric surgery international · 2017Review
- Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: Old and new players.Developmental biology · 2016Review
- Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention.Developmental biology · 2016Review
- Cellular Organization of Neuroimmune Interactions in the Gastrointestinal Tract.Trends in immunology · 2016Review
- Building a second brain in the bowel.The Journal of clinical investigation · 2015Review
- Enteric neuron imbalance and proximal dysmotility in ganglionated intestine of theCellular and molecular gastroenterology and hepatology · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsHand2 is a basic helix-loop-helix transcription factor required for terminal differentiation of enteric neurons. We studied Hand2 haploinsufficient mice, to determine whether reduced expression of Hand2 allows sufficient enteric neurogenesis for survival, but not for development of a normal enteric nervous system (ENS).
methodsEnteric transcripts that encode Hand2 and the neuron-specific embryonic lethal abnormal vision proteins HuB, HuC, and HuD were quantified. Immunocytochemistry was used to identify and quantify neurons. Apoptosis was analyzed with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling procedure. Intracellular microelectrodes were used to record inhibitory junction potentials. Gastrointestinal transit and colonic motility were measured in vivo.
resultsLevels of of enteric Hand2 transcripts were associated with genotypes of mice, in the following order: Hand2(+/+) > Hand2(LoxP/+) > Hand2(+/-) > Hand2(LoxP/-). Parallel reductions were found in expression of HuD and in regional and phenotypic manners. Numbers of neurons, numbers of neuronal nitric oxide synthase(+) and calretinin(+), but not substance P(+) or vasoactive intestinal peptide(+) neurons, decreased. No effects were observed in stomach or cecum. Apoptosis was not detected, consistent with the concept that Hand2 inhibits neuronal differentiation, rather than regulates survival. The amplitude of inhibitory junction potentials in colonic circular muscle was similar in Hand2 wild-type and haploinsufficient mice, although in haploinsufficient mice, the purinergic component was reduced and a nitrergic component appeared. The abnormal ENS of haploinsufficient mice slowed gastrointestinal motility but protected mice against colitis.
conclusionsReduced expression of factors required for development of the ENS can cause defects in the ENS that are subtle enough to escape detection yet cause significant abnormalities in bowel function.
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Registered trials
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