ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
A Phox2- and Hand2-dependent Hand1 cis-regulatory element reveals a unique gene dosage requirement for Hand2 during sympathetic neurogenesis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Amelioration of biased neuronal differentiation in humanized mouse model of valproic acid-induced autism by precisely targeted transcranial magnetic stimulation.Bioengineering & translational medicine · 2025Article
- 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
- Epigenetic Dysregulation inInternational journal of molecular sciences · 2023Review
- Neonatal Deletion ofJournal of cardiovascular development and disease · 2022Article
- Neural Stem Cell-Derived Exosomal Netrin1 Contributes to Neuron Differentiation of Mesenchymal Stem Cells in Therapy of Spinal Bifida Aperta.Stem cells translational medicine · 2022Article
- Recent advances in the developmental origin of neuroblastoma: an overview.Journal of experimental & clinical cancer research : CR · 2022Review
- A show of Hands: Novel and conserved expression patterns of teleost hand paralogs during craniofacial, heart, fin, peripheral nervous system and gut development.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Article
- A Focus on Regulatory Networks Linking MicroRNAs, Transcription Factors and Target Genes in Neuroblastoma.Cancers · 2021Review
- Deletion of aJournal of cardiovascular development and disease · 2021Article
- The diversity of neuronal phenotypes in rodent and human autonomic ganglia.Cell and tissue research · 2020Review
- Mis-Expression of a Cranial Neural Crest Cell-Specific Gene Program in Cardiac Neural Crest Cells Modulates HAND Factor Expression, Causing Cardiac Outflow Tract Phenotypes.Journal of cardiovascular development and disease · 2020Article
- Variation in a Left Ventricle-Specific Hand1 Enhancer Impairs GATA Transcription Factor Binding and Disrupts Conduction System Development and Function.Circulation research · 2019Article
- Sympathetic tales: subdivisons of the autonomic nervous system and the impact of developmental studies.Neural development · 2018Review
- Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Hand factor ablation causes defective left ventricular chamber development and compromised adult cardiac function.PLoS genetics · 2017Article
- Exclusion of Dlx5/6 expression from the distal-most mandibular arches enables BMP-mediated specification of the distal cap.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution.PLoS genetics · 2015Article
- Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development.Oncology letters · 2015Article
- CARM1 regulates astroglial lineage through transcriptional regulation of Nanog and posttranscriptional regulation by miR92a.Molecular biology of the cell · 2015Article
- Hand1 phosphoregulation within the distal arch neural crest is essential for craniofacial morphogenesis.Development (Cambridge, England) · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Neural crest cell specification and differentiation to a sympathetic neuronal fate serves as an important model for neurogenesis and depends upon the function of both bHLH transcription factors, notably Hand2, and homeodomain transcription factors, including Phox2b. Here, we define a 1007 bp cis-regulatory element 5' of the Hand1 gene sufficient to drive reporter expression within the sympathetic chain of transgenic mice. Comparative genomic analyses uncovered evolutionarily conserved consensus-binding sites within this element, which chromatin immunoprecipitation and electrophoretic mobility shift assays confirm are bound by Hand2 and Phox2b. Mutational analyses revealed that the conserved Phox2 and E-box binding sites are necessary for proper cis-regulatory element activity, and expression analyses on both Hand2 conditionally null and hypomorphic backgrounds demonstrate that Hand2 is required for reporter activation in a gene dosage-dependent manner. We demonstrate that Hand2 and Hand1 differentially bind the E-boxes in this cis-regulatory element, establishing molecular differences between these two factors. Finally, we demonstrate that Hand1 is dispensable for normal tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) expression in sympathetic neurons, even when Hand2 gene dosage is concurrently reduced by half. Together, these data define a tissue-specific Hand1 cis-regulatory element controlled by two factors essential for the development of the sympathetic nervous system and provide in vivo regulatory evidence to support previous findings that Hand2, rather than Hand1, is predominantly responsible for regulating TH, DBH, and Hand1 expression in developing sympathetic neurons.
Indexed as
Identifiers
What OpenQuestion holds
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.