Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The mechanisms of neural crest cell induction and specification are highly conserved among vertebrate model organisms, but how similar these mechanisms are in mammalian neural crest cell formation remains open to question. The zinc finger of the cerebellum 1 (ZIC1) transcription factor is considered a core component of the vertebrate gene regulatory network that specifies neural crest fate at the neural plate border. In mouse embryos, however, Zic1 mutation does not cause neural crest defects. Instead, we and others have shown that murine Zic2 and Zic5 mutate to give a neural crest phenotype. Here, we extend this knowledge by demonstrating that murine Zic3 is also required for, and co-operates with, Zic2 and Zic5 during mammalian neural crest specification. At the murine neural plate border (a region of high canonical WNT activity) ZIC2, ZIC3, and ZIC5 function as transcription factors to jointly activate the Foxd3 specifier gene. This function is promoted by SUMOylation of the ZIC proteins at a conserved lysine immediately N-terminal of the ZIC zinc finger domain. In contrast, in the lateral regions of the neurectoderm (a region of low canonical WNT activity) basal ZIC proteins act as co-repressors of WNT/TCF-mediated transcription. Our work provides a mechanism by which mammalian neural crest specification is restricted to the neural plate border. Furthermore, given that WNT signaling and SUMOylation are also features of non-mammalian neural crest specification, it suggests that mammalian neural crest induction shares broad conservation, but altered molecular detail, with chicken, zebrafish, and Xenopus neural crest induction.
Ahmed,
A murine Zic3 transcript with a premature termination codon evades nonsense-mediated decay during axis formation.
2013, Pubmed
Ahmed,
A murine Zic3 transcript with a premature termination codon evades nonsense-mediated decay during axis formation.
2013,
Pubmed
Ahmed,
Systematized reporter assays reveal ZIC protein regulatory abilities are Subclass-specific and dependent upon transcription factor binding site context.
2020,
Pubmed
Ali,
WNT-responsive SUMOylation of ZIC5 promotes murine neural crest cell development, having multiple effects on transcription.
2021,
Pubmed
Arkell,
Genetic, physical, and phenotypic characterization of the Del(13)Svea36H mouse.
2001,
Pubmed
Aruga,
A wide-range phylogenetic analysis of Zic proteins: implications for correlations between protein structure conservation and body plan complexity.
2006,
Pubmed
Badis,
Diversity and complexity in DNA recognition by transcription factors.
2009,
Pubmed
Barratt,
Whole-Mount In Situ Hybridization in Post-Implantation Staged Mouse Embryos.
2020,
Pubmed
Barratt,
Production of Digoxigenin-Labeled Riboprobes for In Situ Hybridization Experiments.
2020,
Pubmed
Barriga,
Animal models for studying neural crest development: is the mouse different?
2015,
Pubmed
,
Xenbase
Bedard,
Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3.
2007,
Pubmed
Bogani,
New semidominant mutations that affect mouse development.
2004,
Pubmed
Brown,
In vitro analysis of partial loss-of-function ZIC2 mutations in holoprosencephaly: alanine tract expansion modulates DNA binding and transactivation.
2005,
Pubmed
Carmona-Fontaine,
Neural crests are actively precluded from the anterior neural fold by a novel inhibitory mechanism dependent on Dickkopf1 secreted by the prechordal mesoderm.
2007,
Pubmed
,
Xenbase
Chang,
Regulation of nuclear receptor and coactivator functions by the carboxyl terminus of ubiquitin-conjugating enzyme 9.
2007,
Pubmed
Chen,
Sumoylation regulates nuclear localization and function of zinc finger transcription factor ZIC3.
2013,
Pubmed
Costa,
Complex SUMO-1 regulation of cardiac transcription factor Nkx2-5.
2011,
Pubmed
Diamand,
Overview of Rodent Zic Genes.
2018,
Pubmed
Downs,
Staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope.
1993,
Pubmed
Elkouby,
Mesodermal Wnt signaling organizes the neural plate via Meis3.
2010,
Pubmed
,
Xenbase
Elms,
Overlapping and distinct expression domains of Zic2 and Zic3 during mouse gastrulation.
2004,
Pubmed
Elms,
Zic2 is required for neural crest formation and hindbrain patterning during mouse development.
2003,
Pubmed
Ewan,
A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription.
2010,
Pubmed
,
Xenbase
Ferrer-Vaquer,
A sensitive and bright single-cell resolution live imaging reporter of Wnt/ß-catenin signaling in the mouse.
2010,
Pubmed
Fujimi,
Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway.
2012,
Pubmed
,
Xenbase
Furushima,
A new murine zinc finger gene, Opr.
2000,
Pubmed
Furushima,
Characterization of Opr deficiency in mouse brain: subtle defects in dorsomedial telencephalon and medioventral forebrain.
2005,
Pubmed
García-Castro,
Ectodermal Wnt function as a neural crest inducer.
2002,
Pubmed
Gareau,
The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition.
2010,
Pubmed
Greco,
Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development.
1996,
Pubmed
Groves,
Setting appropriate boundaries: fate, patterning and competence at the neural plate border.
2014,
Pubmed
,
Xenbase
Hatayama,
Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain.
2008,
Pubmed
Hendriks,
A comprehensive compilation of SUMO proteomics.
2016,
Pubmed
Houtmeyers,
The ZIC gene family encodes multi-functional proteins essential for patterning and morphogenesis.
2013,
Pubmed
,
Xenbase
Inoue,
Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives.
2004,
Pubmed
,
Xenbase
Inoue,
Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo.
2007,
Pubmed
Ishiguro,
Molecular properties of Zic4 and Zic5 proteins: functional diversity within Zic family.
2004,
Pubmed
Jakobs,
Ubc9 fusion-directed SUMOylation (UFDS): a method to analyze function of protein SUMOylation.
2007,
Pubmed
Jakobs,
Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation.
2007,
Pubmed
Kamitani,
Preferential modification of nuclear proteins by a novel ubiquitin-like molecule.
1997,
Pubmed
Kimura-Yoshida,
Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure.
2015,
Pubmed
Koyabu,
Physical and functional interactions between Zic and Gli proteins.
2001,
Pubmed
LaBonne,
Neural crest induction in Xenopus: evidence for a two-signal model.
1998,
Pubmed
,
Xenbase
Lee,
A local Wnt-3a signal is required for development of the mammalian hippocampus.
2000,
Pubmed
Lee,
SUMOylated SoxE factors recruit Grg4 and function as transcriptional repressors in the neural crest.
2012,
Pubmed
,
Xenbase
Lewis,
Reiterated Wnt signaling during zebrafish neural crest development.
2004,
Pubmed
Lim,
The pluripotency regulator Zic3 is a direct activator of the Nanog promoter in ESCs.
2010,
Pubmed
Liu,
Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling.
2013,
Pubmed
Luan,
SUMOylation of Pax7 is essential for neural crest and muscle development.
2013,
Pubmed
Mašek,
Tcf7l1 protects the anterior neural fold from adopting the neural crest fate.
2016,
Pubmed
Milet,
Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest in Xenopus embryos.
2013,
Pubmed
,
Xenbase
Mizugishi,
Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins.
2001,
Pubmed
,
Xenbase
Munemitsu,
Deletion of an amino-terminal sequence beta-catenin in vivo and promotes hyperphosporylation of the adenomatous polyposis coli tumor suppressor protein.
1996,
Pubmed
Nagai,
The expression of the mouse Zic1, Zic2, and Zic3 gene suggests an essential role for Zic genes in body pattern formation.
1997,
Pubmed
Nagai,
Zic2 regulates the kinetics of neurulation.
2000,
Pubmed
Nakaya,
Wnt3a links left-right determination with segmentation and anteroposterior axis elongation.
2005,
Pubmed
Nolan,
A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse.
2000,
Pubmed
Plouhinec,
Pax3 and Zic1 trigger the early neural crest gene regulatory network by the direct activation of multiple key neural crest specifiers.
2014,
Pubmed
,
Xenbase
Poukka,
Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription.
1999,
Pubmed
Pourebrahim,
Transcription factor Zic2 inhibits Wnt/β-catenin protein signaling.
2011,
Pubmed
,
Xenbase
Ramakrishnan,
The Wnt Transcriptional Switch: TLE Removal or Inactivation?
2018,
Pubmed
Saint-Jeannet,
Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a.
1997,
Pubmed
,
Xenbase
Sato,
Neural crest determination by co-activation of Pax3 and Zic1 genes in Xenopus ectoderm.
2005,
Pubmed
,
Xenbase
Simões-Costa,
Establishing neural crest identity: a gene regulatory recipe.
2015,
Pubmed
Simões-Costa,
Dynamic and differential regulation of stem cell factor FoxD3 in the neural crest is Encrypted in the genome.
2012,
Pubmed
Steventon,
Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction.
2009,
Pubmed
,
Xenbase
Stuhlmiller,
Current perspectives of the signaling pathways directing neural crest induction.
2012,
Pubmed
,
Xenbase
Sun,
Wnt3a regulates the development of cardiac neural crest cells by modulating expression of cysteine-rich intestinal protein 2 in rhombomere 6.
2008,
Pubmed
Takada,
Wnt-3a regulates somite and tailbud formation in the mouse embryo.
1994,
Pubmed
Taylor,
SoxE factors function equivalently during neural crest and inner ear development and their activity is regulated by SUMOylation.
2005,
Pubmed
,
Xenbase
Thomsen,
High resolution melt analysis (HRMA); a viable alternative to agarose gel electrophoresis for mouse genotyping.
2012,
Pubmed
Yoshikawa,
Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse.
1997,
Pubmed
Zhao,
β-Catenin/Tcf7l2-dependent transcriptional regulation of GLUT1 gene expression by Zic family proteins in colon cancer.
2019,
Pubmed
van Amerongen,
Knockout mouse models to study Wnt signal transduction.
2006,
Pubmed