Regulation of gene expression downstream of a novel Fgf/Erk pathway during Xenopus development.
Animals
Fibroblast Growth Factors
/ genetics
Gene Expression Regulation, Developmental
MAP Kinase Signaling System
/ genetics
Receptor Protein-Tyrosine Kinases
/ metabolism
Receptors, Fibroblast Growth Factor
/ genetics
Signal Transduction
/ genetics
Transcription Factors
/ genetics
Xenopus laevis
/ metabolism
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
23
11
2022
accepted:
08
05
2023
medline:
23
10
2023
pubmed:
19
10
2023
entrez:
19
10
2023
Statut:
epublish
Résumé
Activation of Map kinase/Erk signalling downstream of fibroblast growth factor (Fgf) tyrosine kinase receptors regulates gene expression required for mesoderm induction and patterning of the anteroposterior axis during Xenopus development. We have proposed that a subset of Fgf target genes are activated in the embyo in response to inhibition of a transcriptional repressor. Here we investigate the hypothesis that Cic (Capicua), which was originally identified as a transcriptional repressor negatively regulated by receptor tyrosine kinase/Erk signalling in Drosophila, is involved in regulating Fgf target gene expression in Xenopus. We characterise Xenopus Cic and show that it is widely expressed in the embryo. Fgf overexpression or ectodermal wounding, both of which potently activate Erk, reduce Cic protein levels in embryonic cells. In keeping with our hypothesis, we show that Cic knockdown and Fgf overexpression have overlapping effects on embryo development and gene expression. Transcriptomic analysis identifies a cohort of genes that are up-regulated by Fgf overexpression and Cic knockdown. We investigate two of these genes as putative targets of the proposed Fgf/Erk/Cic axis: fos and rasl11b, which encode a leucine zipper transcription factor and a ras family GTPase, respectively. We identify Cic consensus binding sites in a highly conserved region of intron 1 in the fos gene and Cic sites in the upstream regions of several other Fgf/Cic co-regulated genes, including rasl11b. We show that expression of fos and rasl11b is blocked in the early mesoderm when Fgf and Erk signalling is inhibited. In addition, we show that fos and rasl11b expression is associated with the Fgf independent activation of Erk at the site of ectodermal wounding. Our data support a role for a Fgf/Erk/Cic axis in regulating a subset of Fgf target genes during gastrulation and is suggestive that Erk signalling is involved in regulating Cic target genes at the site of ectodermal wounding.
Identifiants
pubmed: 37856433
doi: 10.1371/journal.pone.0286040
pii: PONE-D-22-31549
pmc: PMC10586617
doi:
Substances chimiques
Fibroblast Growth Factors
62031-54-3
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Receptors, Fibroblast Growth Factor
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0286040Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J014443/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M011151/1
Pays : United Kingdom
Informations de copyright
Copyright: © 2023 Cowell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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