Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration
During gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high-resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly ex...
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doaj-9a9abedffa894a61829007d9c7f6f24e2021-05-05T21:32:36ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.57779Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigrationShashank Gandhi0https://orcid.org/0000-0002-4081-4338Erica J Hutchins1https://orcid.org/0000-0002-4316-0333Krystyna Maruszko2Jong H Park3Matthew Thomson4Marianne E Bronner5https://orcid.org/0000-0003-4274-1862Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDuring gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high-resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally controlled CRISPR-Cas9-mediated knockouts uncovered two distinct functions of Hmga1 in neural crest development. At the neural plate border, Hmga1 regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where Hmga1 loss reduces cranial crest emigration from the dorsal neural tube independent of Pax7. Interestingly, this is rescued by stabilized ß-catenin, thus implicating Hmga1 as a canonical Wnt activator. Together, our results show that Hmga1 functions in a bimodal manner during neural crest development to regulate specification at the neural plate border, and subsequent emigration from the neural tube via canonical Wnt signaling.https://elifesciences.org/articles/57779neural crestchromatin remodelerWnt signalingspecificationcell migration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shashank Gandhi Erica J Hutchins Krystyna Maruszko Jong H Park Matthew Thomson Marianne E Bronner |
spellingShingle |
Shashank Gandhi Erica J Hutchins Krystyna Maruszko Jong H Park Matthew Thomson Marianne E Bronner Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration eLife neural crest chromatin remodeler Wnt signaling specification cell migration |
author_facet |
Shashank Gandhi Erica J Hutchins Krystyna Maruszko Jong H Park Matthew Thomson Marianne E Bronner |
author_sort |
Shashank Gandhi |
title |
Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration |
title_short |
Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration |
title_full |
Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration |
title_fullStr |
Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration |
title_full_unstemmed |
Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration |
title_sort |
bimodal function of chromatin remodeler hmga1 in neural crest induction and wnt-dependent emigration |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2020-09-01 |
description |
During gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high-resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally controlled CRISPR-Cas9-mediated knockouts uncovered two distinct functions of Hmga1 in neural crest development. At the neural plate border, Hmga1 regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where Hmga1 loss reduces cranial crest emigration from the dorsal neural tube independent of Pax7. Interestingly, this is rescued by stabilized ß-catenin, thus implicating Hmga1 as a canonical Wnt activator. Together, our results show that Hmga1 functions in a bimodal manner during neural crest development to regulate specification at the neural plate border, and subsequent emigration from the neural tube via canonical Wnt signaling. |
topic |
neural crest chromatin remodeler Wnt signaling specification cell migration |
url |
https://elifesciences.org/articles/57779 |
work_keys_str_mv |
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