EphA4-dependent Brachyury expression is required for dorsal mesoderm involution in the <i>Xenopus</i> gastrula

Evren, Sevan; Wen, Jason; Luu, Olivia; Damm, Erich W.; Nagel, Martina; Winklbauer, Rudolf

doi:10.1242/dev.111880

Cited by 26 publications

(28 citation statements)

References 65 publications

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“…Interestingly, the E2a-EnR repressor fusion closely phenocopies the effects of an Xbra-EnR repressor fusion protein, which also causes a shortened axis and reduced axial mesoderm (Conlon et al, 1996; Kitaguchi et al, 2002). These effects are consistent with our observation that E2a directly targets both early axial mesoderm genes such as eomes and xbra , and early morphogenesis genes such as epha4 (Evren et al, 2014; Park et al, 2011). It also supports observations from our RNA-Seq analysis that E2a is normally required for expression of many axial mesoderm genes, including xbra , myod , myf5 , and foxa1 , and that E2a-EnR conversely targets these genes for repression.…”

Section: Resultssupporting

confidence: 92%

“…The activity of E2a as a transcriptional activator has dramatic consequences for gastrulation morphogenesis. Notably, epha4 has recently been shown to regulate dorsal mesoderm involution through xbra (Evren et al, 2014), and so the regulation of these two genes by E2a explains why the loss of E2a has dramatic consequences on gastrulation movements. When E2a is forced to lose its activator role by becoming a repressor, gastrulation movements and axial mesoderm formation are perturbed.…”

Section: Discussionmentioning

confidence: 99%

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E2a Is Necessary for Smad2/3-Dependent Transcription and the Direct Repression of lefty during Gastrulation

Wills

Baker

2015

Developmental Cell

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Summary Transcription factor complexes have varied effects on cell fate and behavior, but how this diversification of function occurs is largely unknown. The Nodal signaling pathway has many biological functions that all converge on the transcription factors Smad2/3. Smad2/3 has many cofactors, and alternative usage of these may provide a mechanism for modulating Smad2/3 function. Here we investigated how perturbation of the cofactor E2a affects global patterns of Smad2/3 binding and gene expression during gastrulation. We find that E2a regulates early development in two ways. E2a changes the position of Smad2/3 binding at the Nodal inhibitor lefty, resulting in direct repression of lefty that is critical for mesendoderm specification. Separately, E2a is necessary to drive transcription of Smad2/3 target genes, including critical regulators of dorsal cell fate and morphogenesis. Overall, we find that E2a functions as both a transcriptional repressor and activator to precisely regulate Nodal signaling.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

E2a Is Necessary for Smad2/3-Dependent Transcription and the Direct Repression of lefty during Gastrulation

Wills

Baker

2015

Developmental Cell

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“…The most investigated signaling is the planar cell polarity (PCP) pathway, which regulates mediolateral cell intercalation during CE (reviewed in Wallingford et al, 2002; Roszko et al, 2009; Skoglund and Keller, 2010; Wallingford, 2012). Different tyrosine kinase signals have also been shown to affect gastrulation morphogenesis (Ataliotis et al, 1995; Conlon and Smith, 1999; Nutt et al, 2001; Nagel et al, 2004; Sivak et al, 2005; Nie and Chang, 2007a, 2007b; Damm and Winklbauer, 2011; Park et al, 2011; Evren et al, 2014). The PCP and the tyrosine kinase pathways may converge to control the activities of Rho family small GTPases to influence cell behaviors (Habas et al, 2001, 2003; Choi and Han, 2002; Pendo-Mendez et al, 2003; Tahinci and Symes, 2003; Ren et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Identification of new regulators of embryonic patterning and morphogenesis in Xenopus gastrulae by RNA sequencing

Popov

Kwon

Crossman

et al. 2017

Developmental Biology

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During early vertebrate embryogenesis, cell fate specification is often coupled with cell acquisition of specific adhesive, polar and/or motile behaviors. In Xenopus gastrulae, tissues fated to form different axial structures display distinct motility. The cells in the early organizer move collectively and directionally toward the animal pole and contribute to anterior mesendoderm, whereas the dorsal and the ventral-posterior trunk tissues surrounding the blastopore of mid-gastrula embryos undergo convergent extension and convergent thickening movements, respectively. While factors regulating cell lineage specification have been described in some detail, the molecular machinery that controls cell motility is not understood in depth. To gain insight into the gene battery that regulates both cell fates and motility in particular embryonic tissues, we performed RNA sequencing (RNA-seq) to investigate differentially expressed genes in the early organizer, the dorsal and the ventral marginal zone of Xenopus gastrulae. We uncovered many known signaling and transcription factors that have been reported to play roles in embryonic patterning during gastrulation. We also identified many uncharacterized genes as well as genes that encoded extracellular matrix (ECM) proteins or potential regulators of actin cytoskeleton. Co-expression of a selected subset of the differentially expressed genes with activin in animal caps revealed that they had distinct ability to block activin-induced animal cap elongation. Most of these factors did not interfere with mesodermal induction by activin, but an ECM protein, EFEMP2, inhibited activin signaling and acted downstream of the activated type I receptor. By focusing on a secreted protein kinase PKDCC1, we showed with overexpression and knockdown experiments that PKDCC1 regulated gastrulation movements as well as anterior neural patterning during early Xenopus development. Overall, our studies identify many differentially expressed signaling and cytoskeleton regulators in different embryonic regions of Xenopus gastrulae and imply their functions in regulating cell fates and/or behaviors during gastrulation.

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“…Another possibility is that the deep cells are engaged in a different, or additional type of motility, associated with the convergence required for involution (e.g. Evren et al 2014).…”

Section: The Interfacial Tension (Ift) Between Deep and Superficial Tmentioning

confidence: 99%

Characterization of convergent thickening, a major convergence force producing morphogenic movement in amphibians

Shook

Wen

Rolo

et al. 2018

Preprint

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SUMMARYWe characterize the morphogenic process of convergent thickening (CT), which occurs in the involuting marginal zone (IMZ) during gastrulation of Xenopus, the African clawed frog. CT was described previously as the tendency of explants of the ventral IMZ of Xenopus to converge their circumblastoporal dimension and thicken their radial dimension (Keller and Danilchik 1988). Here we show that CT occurs from the onset of gastrulation, initially throughout the pre-involution IMZ. We suggest that CT is driven by an increase in the interfacial tension between the deep IMZ and its epithelium, resulting in cells of the deep IMZ tending to minimize their surface area. In explants, this results in a progressive shortening (convergence) of the IMZ along its longer mediolateral axis and thickening in the orthogonal planes, and can generate tensile force (Shook et al. 2018). In vivo, convergence of the annular IMZ generates circumferential tension, closing the blastopore. These results provide the first clear example of a tensile morphogenic force from a Holtfreterian/Steinbergian change in tissue affinity.3

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EphA4-dependent Brachyury expression is required for dorsal mesoderm involution in the Xenopus gastrula

Cited by 26 publications

References 65 publications

E2a Is Necessary for Smad2/3-Dependent Transcription and the Direct Repression of lefty during Gastrulation

E2a Is Necessary for Smad2/3-Dependent Transcription and the Direct Repression of lefty during Gastrulation

Identification of new regulators of embryonic patterning and morphogenesis in Xenopus gastrulae by RNA sequencing

Characterization of convergent thickening, a major convergence force producing morphogenic movement in amphibians

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