ArticleGenes & development2012
Phactr4 regulates directional migration of enteric neural crest through PP1, integrin signaling, and cofilin activity.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
- An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Trial
- Tracing the enteric neural crest cell pathway from origin to colonization: insights into Hirschsprung's disease.Molecular biology reports · 2025Review
- Phactr4 influences macrophage lamellipodial structure and dynamics through Arp2/3 complex and Ezrin regulation.bioRxiv : the preprint server for biology · 2025Article
- THUMPD3 regulates alternative splicing of ECM transcripts in human lung cancer cells and promotes proliferation and migration.PloS one · 2024Article
- TMEM132A ensures mouse caudal neural tube closure and regulates integrin-based mesodermal migration.Development (Cambridge, England) · 2022Article
- Phostensin enables lymphocyte integrin activation and population of peripheral lymphoid organs.The Journal of experimental medicine · 2022Article
- Focal adhesion-mediated cell anchoring and migration: from in vitro to in vivo.Development (Cambridge, England) · 2022Article
- Discovery of Novel Circulating Immune Complexes in Lupus Nephritis Using Immunoproteomics.Frontiers in immunology · 2022Article
- OPRD1 SNPs associated with opioid addiction are cis-eQTLs for the phosphatase and actin regulator 4 gene, PHACTR4, a mediator of cytoskeletal dynamics.Translational psychiatry · 2021Article
- Mutation in PHACTR1 associated with multifocal epilepsy with infantile spasms and hypsarrhythmia.Clinical genetics · 2021Article
- Article
- Protein phosphatase 1 activity controls a balance between collective and single cell modes of migration.eLife · 2020Article
- The road best traveled: Neural crest migration upon the extracellular matrix.Seminars in cell & developmental biology · 2020Review
- Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1).FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Increased miR-214 expression suppresses cell migration and proliferation in Hirschsprung disease by interacting with PLAGL2.Pediatric research · 2019Article
- In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.Developmental cell · 2019Article
- Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Combinatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulation by ADAR1 in Gastric Cancer.Digestive diseases and sciences · 2018Article
- NCAM affects directional lamellipodia formation of BMSCs via β1 integrin signal-mediated cofilin activity.Molecular and cellular biochemistry · 2017Article
- Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: Old and new players.Developmental biology · 2016Review
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Hirschsprung disease (HSCR) is caused by a reduction of enteric neural crest cells (ENCCs) in the gut and gastrointestinal blockage. Knowledge of the genetics underlying HSCR is incomplete, particularly genes that control cellular behaviors of ENCC migration. Here we report a novel regulator of ENCC migration in mice. Disruption of the Phactr4 gene causes an embryonic gastrointestinal defect due to colon hypoganglionosis, which resembles human HSCR. Time-lapse imaging of ENCCs within the embryonic gut demonstrates a collective cell migration defect. Mutant ENCCs show undirected cellular protrusions and disrupted directional and chain migration. Phactr4 acts cell-autonomously in ENCCs and colocalizes with integrin and cofilin at cell protrusions. Mechanistically, we show that Phactr4 negatively regulates integrin signaling through the RHO/ROCK pathway and coordinates protein phosphatase 1 (PP1) with cofilin activity to regulate cytoskeletal dynamics. Strikingly, lamellipodia formation and in vivo ENCC chain migration defects are rescued by inhibition of ROCK or integrin function. Our results demonstrate a previously unknown pathway in ENCC collective migration in vivo and provide new candidate genes for human genetic studies of HSCR.
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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.