ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2001
Conserved function of Caenorhabditis elegans UNC-30 and mouse Pitx2 in controlling GABAergic neuron differentiation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 69 citations in OpenAlex.
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- UNC-30/PITX coordinates neurotransmitter identity with postsynaptic GABA receptor clustering.Development (Cambridge, England) · 2024Article
- Molecular analyses of zebrafish V0v spinal interneurons and identification of transcriptional regulators downstream of Evx1 and Evx2 in these cells.Neural development · 2023Article
- Modulation of protease expression by the transcription factor Ptx1/PITX regulates protein quality control during aging.Cell reports · 2023Article
- Immunity-longevity tradeoff neurally controlled by GABAergic transcription factor PITX1/UNC-30.Cell reports · 2021Article
- GABAergic synapses suppress intestinal innate immunity via insulin signaling inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Divergent Nodes of Non-autonomous UPRCell reports · 2020Article
- Dynamic neurotransmitter specific transcription factor expression profiles duringBiology open · 2020Article
- Systematic evaluation of C. elegans lincRNAs with CRISPR knockout mutants.Genome biology · 2019Article
- Role of tyramine in calcium dynamics of GABAergic neurons and escape behavior inZoological letters · 2018Article
- Odorant Sensory Input Modulates DNA Secondary Structure Formation and Heterogeneous Ribonucleoprotein Recruitment on the Tyrosine Hydroxylase and Glutamic Acid Decarboxylase 1 Promoters in the Olfactory Bulb.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Cerberus-Nodal-Lefty-Pitx signaling cascade controls leftProceedings of the National Academy of Sciences of the United States of America · 2017Article
- The homeodomain transcription factor Phox2 in the stellate ganglion of the squid Loligo pealei.Biology open · 2015Article
- Pleiotropic and isoform-specific functions for Pitx2 in superior colliculus and hypothalamic neuronal development.Molecular and cellular neurosciences · 2013Article
- Functional evolution of mammalian odorant receptors.PLoS genetics · 2012Article
- Spatial and temporal lineage analysis of a Pitx3-driven Cre-recombinase knock-in mouse model.PloS one · 2012Article
- GABAergic and glutamatergic identities of developing midbrain Pitx2 neurons.Developmental dynamics : an official publication of the American Association of Anatomists · 2011Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
We are taking a cross-species approach to identify genes that are required for mammalian GABAergic neuron differentiation. On the basis of homeodomain similarity, the vertebrate Pitx genes appear to be orthologs of unc-30, a Caenorhabditis elegans gene necessary for differentiation of the GABAergic phenotype of type D neurons. One of the Pitx genes, Pitx2, is expressed in regions of GABAergic neurogenesis in the mammalian brain. These observations led us to test the functional conservation of the mouse Pitx2 and worm unc-30 genes using a rescue assay. Pitx2 rescues the GABAergic differentiation defect and partially rescues the axon guidance and behavioral phenotypes of unc-30 mutants, indicating a high degree of functional conservation between these evolutionarily related genes. Previous studies show that UNC-30 directly regulates the unc-25/glutamate decarboxylase gene that encodes the enzyme for GABA synthesis. We find that the promoter regions of the mouse and human genes coding for the 67 kDa glutamate decarboxylase (Gad1) also contain binding sites matching the UNC-30/Pitx2 consensus binding site sequence. We show that these sites specifically bind to Pitx2 protein in vitro and that in transfected neuroblastoma cells, the Pitx2 binding sites contribute to the basal activity of the Gad1 promoter. Furthermore, in cotransfection experiments, we find that Pitx2 strongly activates the Gad1 promoter. These results indicate that Pitx2 may regulate Gad1 expression in mammals, suggesting a new role for this key developmental transcription factor as a regulator of GABAergic differentiation during mammalian neural development. Our results suggest that some of the mechanisms regulating GABAergic differentiation are evolutionarily conserved.
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11517269PMC6763078W2131937765What 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.