ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Brn3a and Islet1 act epistatically to regulate the gene expression program of sensory differentiation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 117 citations in OpenAlex.
- Induction of human pruriceptors from pluripotent stem cells via transcription factors.Stem cell reports · 2026Article
- PBAE nanoparticle-mediated delivery of ASCL1 and NGN2 genes for astroglia-to-neuron reprogramming to remodel glial scar for spinal cord injury repair.Stem cell research & therapy · 2026Article
- Derivation and analysis of human somatic sensory neuron subtypes facilitated through fluorescent hPSC reporters.Stem cell reports · 2026Article
- BRN3A, a transcription factor, regulates the expression of genes involved in biological processes shaping the HPV induced cervical cancer.Genes & genomics · 2025Article
- Runx3, Brn3a and Isl1 interplay orchestrates the transcriptional program in the early stages of proprioceptive neuron development.PLoS genetics · 2024Article
- Molecular regulation of axon termination in mechanosensory neurons.Development (Cambridge, England) · 2024Review
- Neph1 is required for neurite branching and is negatively regulated by the PRRXL1 homeodomain factor in the developing spinal cord dorsal horn.Neural development · 2024Article
- CAbiNet: joint clustering and visualization of cells and genes for single-cell transcriptomics.Nucleic acids research · 2024Article
- Article
- ISL1 and POU4F1 Directly Interact to Regulate the Differentiation and Survival of Inner Ear Sensory Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Rapid and efficient generation of a transplantable population of functional retinal ganglion cells from fibroblasts.Cell proliferation · 2024Article
- Identification of multiple transcription factor genes potentially involved in the development of electrosensoryFrontiers in cell and developmental biology · 2024Article
- Intervertebral disc human nucleus pulposus cells associated with back pain trigger neurite outgrowth in vitro and pain behaviors in rats.Science translational medicine · 2023Article
- Influencers in the Somatosensory System: Extrinsic Control of Sensory Neuron Phenotypes.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2023Review
- EGR4 is critical for cell-fate determination and phenotypic maintenance of geniculate ganglion neurons underlying sweet and umami taste.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neuro-mesodermal assembloids recapitulate aspects of peripheral nervous system development in vitro.Stem cell reports · 2023Article
- Early Steps towards Hearing: Placodes and Sensory Development.International journal of molecular sciences · 2023Review
- Global analyses of mRNA expression in human sensory neurons reveal eIF5A as a conserved target for inflammatory pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Robust regulatory architecture of pan-neuronal gene expression.Current biology : CB · 2022Article
- Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The combinatorial expression of transcription factors frequently marks cellular identity in the nervous system, yet how these factors interact to determine specific neuronal phenotypes is not well understood. Sensory neurons of the trigeminal ganglion (TG) and dorsal root ganglia (DRG) coexpress the homeodomain transcription factors Brn3a and Islet1, and past work has revealed partially overlapping programs of gene expression downstream of these factors. Here we examine sensory development in Brn3a/Islet1 double knock-out (DKO) mice. Sensory neurogenesis and the formation of the TG and DRG occur in DKO embryos, but the DRG are dorsally displaced, and the peripheral projections of the ganglia are markedly disturbed. Sensory neurons in DKO embryos show a profound loss of all early markers of sensory subtypes, including the Ntrk neurotrophin receptors, and the runt-family transcription factors Runx1 and Runx3. Examination of global gene expression in the E12.5 DRG of single and double mutant embryos shows that Brn3a and Islet1 are together required for nearly all aspects of sensory-specific gene expression, including several newly identified sensory markers. On a majority of targets, Brn3a and Islet1 exhibit negative epistasis, in which the effects of the individual knock-out alleles are less than additive in the DKO. Smaller subsets of targets exhibit positive epistasis, or are regulated exclusively by one factor. Brn3a/Islet1 double mutants also fail to developmentally repress neurogenic bHLH genes, and in vivo chromatin immunoprecipitation shows that Islet1 binds to a known Brn3a-regulated enhancer in the neurod4 gene, suggesting a mechanism of interaction between these genes.
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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.