ArticleHuman molecular genetics2021
Loss of Zic3 impairs planar cell polarity leading to abnormal left-right signaling, heart defects and neural tube defects.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Expanding the phenotypic spectrum associated with ZIC1 variants: A neurodevelopmental disorder with and without craniosynostosis.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Prenatal and postnatal manifestations of WBP11-related disorder in Chinese patients: expanding the phenotypic and mutational spectrum.Human genomics · 2026Article
- Broadening horizons: new links between cilia and heart development and disease.Frontiers in cardiovascular medicine · 2026Review
- Linking Planar Cell Polarity to Mechanotransduction During Morphogenesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- In vivo modeling of lethal congenital contracture syndrome 1 suggests pathomechanisms in cellular stress responses.The FEBS journal · 2025Article
- Gpr101 expression during early stages of murine development.Gene expression patterns : GEP · 2025Article
- Exploring Ciliary Mechanisms in the Causation of Hydrocephalus in Humans-Similarities and Differences from Animal Models.Journal of molecular neuroscience : MN · 2025Review
- A CRISPR mis-insertion in the Zic3 5'UTR inhibits in vivo translation and is predicted to result in formation of an mRNA stem-loop hairpin.Biology open · 2025Article
- Molecular mechanism, diagnosis, and treatment of VACTERL association.Frontiers in pediatrics · 2025Review
- Breaking Left-Right Symmetry by the Interplay of Planar Cell Polarity, Calcium Signaling and Cilia.Cells · 2024Review
- ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency.Nature communications · 2024Article
- Canonical and Non-Canonical Wnt Signaling Generates Molecular and Cellular Asymmetries to Establish Embryonic Axes.Journal of developmental biology · 2024Review
- Single-cell RNA sequencing reveals the transcriptional heterogeneity of Tbx18-positive cardiac cells during heart development.Functional & integrative genomics · 2024Article
- Deficiency ofFrontiers in cell and developmental biology · 2023Article
- Human-gained heart enhancers are associated with species-specific cardiac attributes.Nature cardiovascular research · 2022Article
- The genetic landscape of cardiovascular left-right patterning defects.Current opinion in genetics & development · 2022Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Loss of function of ZIC3 causes heterotaxy (OMIM #306955), a disorder characterized by organ laterality defects including complex heart defects. Studies using Zic3 mutant mice have demonstrated that loss of Zic3 causes heterotaxy due to defects in establishment of left-right (LR) signaling, but the mechanistic basis for these defects remains unknown. Here, we demonstrate Zic3 null mice undergo cilia positioning defects at the embryonic node consistent with impaired planar cell polarity (PCP). Cell-based assays demonstrate that ZIC3 must enter the nucleus to regulate PCP and identify multiple critical ZIC3 domains required for regulation of PCP signaling. Furthermore, we show that Zic3 displays a genetic interaction with the PCP membrane protein Vangl2 and the PCP effector genes Rac1 and Daam1 resulting in increased frequency and severity of neural tube and heart defects. Gene and protein expression analyses indicate that Zic3 null embryos display disrupted expression of PCP components and reduced phosphorylation of the core PCP protein DVL2 at the time of LR axis determination. These results demonstrate that ZIC3 interacts with PCP signaling during early development, identifying a novel role for this transcription factor, and adding additional evidence about the importance of PCP function for normal LR patterning and subsequent heart development.
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