SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification
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...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10437 |
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| author | Helen M. Bellchambers Kristen S. Barratt Koula E. M. Diamand Ruth M. Arkell |
| author_facet | Helen M. Bellchambers Kristen S. Barratt Koula E. M. Diamand Ruth M. Arkell |
| author_sort | Helen M. Bellchambers |
| collection | DOAJ |
| description | 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, <i>Zic1</i> mutation does not cause neural crest defects. Instead, we and others have shown that murine <i>Zic2</i> and <i>Zic5</i> mutate to give a neural crest phenotype. Here, we extend this knowledge by demonstrating that murine <i>Zic3</i> is also required for, and co-operates with, <i>Zic2</i> and <i>Zic5</i> 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 <i>Foxd3</i> 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 <i>Xenopus</i> neural crest induction. |
| first_indexed | 2024-03-10T06:59:52Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:59:52Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6c1cc9d533ce47beaa40749f91e600032023-11-22T16:09:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191043710.3390/ijms221910437SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell SpecificationHelen M. Bellchambers0Kristen S. Barratt1Koula E. M. Diamand2Ruth M. Arkell3Early Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaEarly Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaEarly Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaEarly Mammalian Development Laboratory, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, AustraliaThe 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, <i>Zic1</i> mutation does not cause neural crest defects. Instead, we and others have shown that murine <i>Zic2</i> and <i>Zic5</i> mutate to give a neural crest phenotype. Here, we extend this knowledge by demonstrating that murine <i>Zic3</i> is also required for, and co-operates with, <i>Zic2</i> and <i>Zic5</i> 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 <i>Foxd3</i> 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 <i>Xenopus</i> neural crest induction.https://www.mdpi.com/1422-0067/22/19/10437TCF<i>Foxd3</i>post-translational modificationtranscription factorco-factorZIC |
| spellingShingle | Helen M. Bellchambers Kristen S. Barratt Koula E. M. Diamand Ruth M. Arkell SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification International Journal of Molecular Sciences TCF <i>Foxd3</i> post-translational modification transcription factor co-factor ZIC |
| title | SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification |
| title_full | SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification |
| title_fullStr | SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification |
| title_full_unstemmed | SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification |
| title_short | SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification |
| title_sort | sumoylation potentiates zic protein activity to influence murine neural crest cell specification |
| topic | TCF <i>Foxd3</i> post-translational modification transcription factor co-factor ZIC |
| url | https://www.mdpi.com/1422-0067/22/19/10437 |
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