Positioning a multifunctional basic helix-loop-helix transcription factor within the Ciona notochord gene regulatory network

Kugler, Jamie E.; Wu, Yushi; Katikala, Lavanya; Passamaneck, Yale J.; Addy, Jermyn; Caballero, Natalia; Oda-Ishii, Izumi; Maguire, Julie E.; Li, Raymond; Gregorio, Anna Di

doi:10.1016/j.ydbio.2019.01.002

Cited by 10 publications

(20 citation statements)

References 59 publications

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“…In addition to sharing some of its target genes with Ci-Bra, Cr-Xbp1 shares part of these notochord genes with Tbx2/3 ( José-Edwards et al, 2013 ), and ChIP-chip experiments indicate that the genomic loci of some of the Cr-Xbp1 notochord targets are occupied by Foxa.a in early embryos ( Kubo et al, 2010 ; Supplementary file 1 ). No overlap was found between the notochord genes downstream of Cr-Xbp1 and those controlled by another node of the Ciona notochord GRN, the ascidian-specific transcription factor Bhlh-tun1 ( Kugler et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…The pressure exerted on the rigid notochordal sheath by the lumen provides the tail with a hydrostatic skeleton along which rest the muscle cells flanking the notochord, whose contractions enable the larvae to swim ( Bone, 1992 ; Kier, 2012 ). In addition to Brachyury and Foxa2 (Foxa.a in Ciona ) orthologs, other transcription factors are expressed in the Ciona notochord ( Satou et al, 2001 ; Imai et al, 2004 ; Kugler et al, 2008 ; Kugler et al, 2019 ; José-Edwards et al, 2011 ; José-Edwards et al, 2013 ; Reeves et al, 2017 ). Among them is the Ciona counterpart of X-box binding protein 1 (Xbp1) ( Kugler et al, 2008 ), a basic leucine-zipper transcription factor that regulates the unfolded protein response (UPR) ( Mai and Breeden, 1997 ; Yoshida et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

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Xbp1 and Brachyury establish an evolutionarily conserved subcircuit of the notochord gene regulatory network

Devotta

José-Edwards

et al. 2022

eLife

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Gene regulatory networks coordinate the formation of organs and structures that compose the evolving body plans of different organisms. We are using a simple chordate model, the Ciona embryo, to investigate the essential gene regulatory network that orchestrates morphogenesis of the notochord, a structure necessary for the proper development of all chordate embryos. Although numerous transcription factors expressed in the notochord have been identified in different chordates, several of them remain to be positioned within a regulatory framework. Here we focus on Xbp1, a transcription factor expressed during notochord formation in Ciona and other chordates. Through the identification of Xbp1-downstream notochord genes in Ciona, we found evidence of the early co-option of genes involved in the unfolded protein response to the notochord developmental program. We report the regulatory interplay between Xbp1 and Brachyury, and by extending these results to Xenopus, we show that Brachyury and Xbp1 form a cross-regulatory subcircuit of the notochord gene regulatory network that has been consolidated during chordate evolution.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Xbp1 and Brachyury establish an evolutionarily conserved subcircuit of the notochord gene regulatory network

Devotta

José-Edwards

et al. 2022

eLife

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“…7 C). Characteristic temporal expression profiles have previously been identified by in situ hybridization for select notochord genes, [ 78 – 80 , 83 , 84 , 86 , 89 , 90 ] but the genome-wide transcriptional profiling performed here allows the comprehensive identification of distinct suites of genes that co-vary in expression in the notochord over time. A similar set of distinct temporal waves was seen when clustering the temporal expression profiles of the notochord-enriched transcription factors alone (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-cell analysis of cell fate bifurcation in the chordate Ciona

2021

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Background Inductive signaling interactions between different cell types are a major mechanism for the further diversification of embryonic cell fates. Most blastomeres in the model chordate Ciona robusta become restricted to a single predominant fate between the 64-cell and mid-gastrula stages. The deeply stereotyped and well-characterized Ciona embryonic cell lineages allow the transcriptomic analysis of newly established cell types very early in their divergence from sibling cell states without the pseudotime inference needed in the analysis of less synchronized cell populations. This is the first ascidian study to use droplet scRNAseq with large numbers of analyzed cells as early as the 64-cell stage when major lineages such as primary notochord first become fate restricted. Results and conclusions We identify 59 distinct cell states, including new subregions of the b-line neural lineage and the early induction of the tail tip epidermis. We find that 34 of these cell states are directly or indirectly dependent on MAPK-mediated signaling critical to early Ciona patterning. Most of the MAPK-dependent bifurcations are canalized with the signal-induced cell fate lost upon MAPK inhibition, but the posterior endoderm is unique in being transformed into a novel state expressing some but not all markers of both endoderm and muscle. Divergent gene expression between newly bifurcated sibling cell types is dominated by upregulation in the induced cell type. The Ets family transcription factor Elk1/3/4 is uniquely upregulated in nearly all the putatively direct inductions. Elk1/3/4 upregulation together with Ets transcription factor binding site enrichment analysis enables inferences about which bifurcations are directly versus indirectly controlled by MAPK signaling. We examine notochord induction in detail and find that the transition between a Zic/Ets-mediated regulatory state and a Brachyury/FoxA-mediated regulatory state is unexpectedly late. This supports a “broad-hourglass” model of cell fate specification in which many early tissue-specific genes are induced in parallel to key tissue-specific transcriptional regulators via the same set of transcriptional inputs.

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“…We compared the expression level from 64-cell through hatching larva of the TFs which were upregulated in muscle, mesenchyme and endoderm compared to their sibling cell types at their initial bifurcation. We find that these TFs generally fall into one of two categories: some are expressed for only a short time window whereas others show persistent and/or increasing expression ( Figure 5 The Ciona notochord has been intensively studied as a model for understanding tissue-specific gene expression and morphogenesis [63][64][65][66][67][68][69][70][71][72]. This is the first study to To analyze if these genes were in fact notochord specific, we extracted the average expression value of each of these genes in all of the other cell clusters at the 64-cell stage.…”

Section: Some Fgf Dependent Cell Types Are Not Transfated To Sibling mentioning

confidence: 98%

“…Much like in the endoderm, muscle, and mesenchyme, we find that the DE TFs are either expressed strongly in a short time frame around fate induction or are stably expressed and increase their expression over time (Figure 6 C).The notochord exhibits distinct waves of transcriptionTo further characterize the temporal dynamics of the Ciona notochord transcriptome, we plotted the notochord expression levels over time of all the genes that are enriched in the notochord compared to other non-notochord tissues at each stage.Hierarchical clustering of these notochord enriched genes revealed 5 relatively distinct temporal waves of expression (Figure 6D-E). Characteristic temporal expression profiles have previously been identified by in situ hybridization for select notochord genes,[65][66][67]70,71,73,76,77] but the genome-wide transcriptional profiling performed here allows the comprehensive identification of distinct suites of genes that co-vary in expression in the notochord over time. A similar set of distinct temporal waves was seen when clustering the temporal expression profiles of the notochord-enriched transcription factors alone, suggesting that these waves might be controlled by distinct TFs or combinations of TFs acting in a differentiation cascade.…”

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confidence: 99%

Single-cell analysis of cell fate bifurcation in the chordateCiona

Winkley

Reeves

Veeman

2020

Preprint

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Inductive signaling interactions between different cell types are a major mechanism for the further diversification of embryonic cell fates. Most blastomeres in the model chordate Ciona robusta become restricted to a single predominant fate between the 64-cell and mid-gastrula stages. We used single-cell RNAseq spanning this period to identify 53 distinct cell states, 25 of which are dependent on a MAPK-mediated signal critical to early Ciona patterning. Divergent gene expression between newly bifurcated sibling cell types is dominated by upregulation in the induced cell type. These upregulated genes typically include numerous transcription factors and not just one or two key regulators. The Ets family transcription factor Elk1/3/4 is upregulated in almost all the putatively direct inductions, indicating that it may act in an FGF-dependent feedback loop. We examine several bifurcations in detail and find support for a 'broad-hourglass' model of cell fate specification in which many genes are induced in parallel to key tissue-specific transcriptional regulators via the same set of transcriptional inputs.

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Positioning a multifunctional basic helix-loop-helix transcription factor within the Ciona notochord gene regulatory network

Cited by 10 publications

References 59 publications

Xbp1 and Brachyury establish an evolutionarily conserved subcircuit of the notochord gene regulatory network

Xbp1 and Brachyury establish an evolutionarily conserved subcircuit of the notochord gene regulatory network

Single-cell analysis of cell fate bifurcation in the chordate Ciona

Single-cell analysis of cell fate bifurcation in the chordateCiona

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