Iterative and Complex Asymmetric Divisions Control Cell Volume Differences in Ciona Notochord Tapering

Winkley, Konner; Ward, Spencer; Reeves, Wendy; Veeman, Michael

doi:10.1016/j.cub.2019.08.056

Cited by 20 publications

(17 citation statements)

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“…2C). Interestingly, a recent study of the developing notochord of the chordate Ciona revealed that different notochord blastomeres utilize a combination of polarized displacement of mitotic spindles, mother cell shape and post-anaphase mechanisms between different rounds of cell division to establish unequal sibling cell size (Winkley et al, 2019).…”

Section: Spindle and Cell Size Asymmetrymentioning

confidence: 99%

Principles and mechanisms of asymmetric cell division

2020

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Asymmetric cell division (ACD) is an evolutionarily conserved mechanism used by prokaryotes and eukaryotes alike to control cell fate and generate cell diversity. A detailed mechanistic understanding of ACD is therefore necessary to understand cell fate decisions in health and disease. ACD can be manifested in the biased segregation of macromolecules, the differential partitioning of cell organelles, or differences in sibling cell size or shape. These events are usually preceded by and influenced by symmetry breaking events and cell polarization. In this Review, we focus predominantly on cell intrinsic mechanisms and their contribution to cell polarization, ACD and binary cell fate decisions. We discuss examples of polarized systems and detail how polarization is established and, whenever possible, how it contributes to ACD. Established and emerging model organisms will be considered alike, illuminating both welldocumented and underexplored forms of polarization and ACD.

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Section: Spindle and Cell Size Asymmetrymentioning

confidence: 99%

Principles and mechanisms of asymmetric cell division

2020

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“…The anterior 32 cells in the intercalated notochord are derived from the primary notochord founder blastomeres, whereas the posterior 8 cells are derived from the secondary founder cells [41,42]. There is considerable stochasticity in the intercalation of the primary notochord cells, but the descendants of A8.5 and A8.6 are biased towards the anterior and the descendants of A8.13 and A8.14 are biased towards the posterior of the primary notochord [42,43]. It is likely that these AP differences in reporter construct expression reflect subtle expression differences between different notochord founder cells.…”

Section: Endogenous Bra Expression Follows Similar Responses To U0126mentioning

confidence: 99%

Ciona Brachyury proximal and distal enhancers have different FGF dose-response relationships

et al. 2021

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Many genes are regulated by two or more enhancers that drive similar expression patterns. Evolutionary theory suggests that these seemingly redundant enhancers must have functionally important differences. In the simple ascidian chordate Ciona, the transcription factor Brachyury is induced exclusively in the presumptive notochord downstream of lineage specific regulators and FGF-responsive Ets family transcription factors. Here we exploit the ability to finely titrate FGF signaling activity via the MAPK pathway using the MEK inhibitor U0126 to quantify the dependence of transcription driven by different Brachyury reporter constructs on this direct upstream regulator. We find that the more powerful promoter-adjacent proximal enhancer and a weaker distal enhancer have fundamentally different dose-response relationships to MAPK inhibition. The Distal enhancer is more sensitive to MAPK inhibition but shows a less cooperative response, whereas the Proximal enhancer is less sensitive and more cooperative. A longer construct containing both enhancers has a complex dose-response curve that supports the idea that the proximal and distal enhancers are moderately super-additive. We show that the overall expression loss from intermediate doses of U0126 is not only a function of the fraction of cells expressing these reporters, but also involves graded decreases in expression at the single-cell level. Expression of the endogenous gene shows a comparable dose-response relationship to the full length reporter, and we find that different notochord founder cells are differentially sensitive to MAPK inhibition. Together, these results indicate that although the two Brachyury enhancers have qualitatively similar expression patterns, they respond to FGF in quantitatively different ways and act together to drive high levels of Brachyury expression with a characteristic input/output relationship. This indicates that they are fundamentally not equivalent genetic elements.

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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: 97%

Single-cell analysis of cell fate bifurcation in the chordateCiona

Winkley

Reeves

Veeman

2020

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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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Iterative and Complex Asymmetric Divisions Control Cell Volume Differences in Ciona Notochord Tapering

Cited by 20 publications

References 50 publications

Principles and mechanisms of asymmetric cell division

Principles and mechanisms of asymmetric cell division

Ciona Brachyury proximal and distal enhancers have different FGF dose-response relationships

Single-cell analysis of cell fate bifurcation in the chordateCiona

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