ArticleDevelopment (Cambridge, England)2011
Targeted deletion of Hand2 in enteric neural precursor cells affects its functions in neurogenesis, neurotransmitter specification and gangliogenesis, causing functional aganglionosis.
Article in Development (Cambridge, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 62 citations in OpenAlex.
- Dysregulation of neuronal androgen receptor signaling by divergent collaborative transcription factors in Alzheimer's disease.iScience · 2026Article
- Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects.Development (Cambridge, England) · 2025Article
- Integrative analysis of ultra-deep RNA-seq reveals alternative promoter usage as a mechanism of activating oncogenic programmes during prostate cancer progression.Nature cell biology · 2024Article
- Identification and characterization of Hand2 upstream genomic enhancers active in developing stomach and limbs.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Manifold Interpolating Optimal-Transport Flows for Trajectory Inference.Advances in neural information processing systems · 2022Article
- Regional cytoarchitecture of the adult and developing mouse enteric nervous system.Current biology : CB · 2022Article
- A neural crest cell isotropic-to-nematic phase transition in the developing mammalian gut.Communications biology · 2021Article
- Article
- Synaptic Components, Function and Modulation Characterized by GCaMP6f CaFrontiers in physiology · 2021Article
- scRNA-Seq Reveals New Enteric Nervous System Roles for GDNF, NRTN, and TBX3.Cellular and molecular gastroenterology and hepatology · 2021Article
- Transcription factor Ptf1a in development, diseases and reprogramming.Cellular and molecular life sciences : CMLS · 2019Review
- Muscularis macrophage development in the absence of an enteric nervous system.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- 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
- Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm.eLife · 2016Article
- Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: Old and new players.Developmental biology · 2016Review
- Neural crest requires Impdh2 for development of the enteric nervous system, great vessels, and craniofacial skeleton.Developmental biology · 2016Article
- SMN deficiency disrupts gastrointestinal and enteric nervous system function in mice.Human molecular genetics · 2015Article
- Ascl1 phospho-status regulates neuronal differentiation in a Xenopus developmental model of neuroblastoma.Disease models & mechanisms · 2015Article
- Immunostaining to visualize murine enteric nervous system development.Journal of visualized experiments : JoVE · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Targeted deletion of the bHLH DNA-binding protein Hand2 in the neural crest, impacts development of the enteric nervous system (ENS), possibly by regulating the transition from neural precursor cell to neuron. We tested this hypothesis by targeting Hand2 deletion in nestin-expressing neural precursor (NEP) cells. The mutant mice showed abnormal ENS development, resulting in lethal neurogenic pseudo-obstruction. Neurogenesis of neurons derived from NEP cells identified a second nestin non-expressing neural precursor (NNEP) cell in the ENS. There was substantial compensation for the loss of neurons derived from the NEP pool by the NNEP pool but this was insufficient to abrogate the negative impact of Hand2 deletion. Hand2-mediated regulation of proliferation affected both neural precursor and neuron numbers. Differentiation of glial cells derived from the NEP cells was significantly decreased with no compensation from the NNEP pool of cells. Our data indicate differential developmental potential of NEPs and NNEPs; NNEPs preferentially differentiate as neurons, whereas NEPs give rise to both neurons and glial cells. Deletion of Hand2 also resulted in complete loss of NOS and VIP and a significant decrease in expression of choline acetyltransferase and calretinin, demonstrating a role for Hand2 in neurotransmitter specification and/or expression. Loss of Hand2 resulted in a marked disruption of the developing neural network, exemplified by lack of a myenteric plexus and extensive overgrowth of fibers. Thus, Hand2 is essential for neurogenesis, neurotransmitter specification and neural network patterning in the developing ENS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.