Evolutionarily conserved requirement of Cdx for post-occipital tissue emergence

Rooijen, Carina van; Simmini, Salvatore; Bialecka, Monika; Neijts, Roel; Ven, Cesca van de; Beck, Felix; Deschamps, Jacqueline

doi:10.1242/dev.079848

Cited by 62 publications

(68 citation statements)

References 44 publications

(69 reference statements)

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“…Therefore, they do more than merely confer axial identity to the emerging tissues. Cdx genes are required in a dosage-dependent manner for the generation of post-occipital embryonic axial tissues (van Rooijen et al 2012). Cdx2 transcriptionally activates Wnt and Fgf signaling pathway components in posterior embryonic tissues ) and thus maintains the proficiency of the axial progenitor niche.…”

Section: A Link Between the Hox Clock And The Somitic Clock?mentioning

confidence: 99%

Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

2017

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Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work of Ed Lewis in 1978. Here we discuss recent advances in our understanding of this phenomenon in relation to novel concepts associated with large-scale regulation and chromatin structure during the development of both axial and limb patterns. We further discuss how this sequential transcriptional activation marks embryonic stem cell-like axial progenitors in mammals and, consequently, how a temporal genetic system is further translated into spatial coordinates via the fate of these progenitors. In this context, we argue the benefit and necessity of implementing this unique mechanism as well as the difficulty in evolving an alternative strategy to deliver this critical positional information.

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Section: A Link Between the Hox Clock And The Somitic Clock?mentioning

confidence: 99%

Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

2017

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“…Hox genes also regulate components of retinoid signaling (Aldh1a2/Raldh2 and Rarb) to set up feedback loops that reinforce positive cross-talk between Hox expression and RA signaling (Serpente et al 2005;Vitobello et al 2011). In addition to the direct effects of retinoids on Hox expression, RA modulates the expression domains of the Cdx transcription factors, and these in turn bind to cis-elements in the Hox clusters to regulate axial expression (Houle et al 2000(Houle et al , 2003Lohnes 2003;Young et al 2009;van de Ven et al 2011;van Rooijen et al 2012).…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells

et al. 2015

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The clustered Hox genes, which are highly conserved across metazoans, encode homeodomain-containing transcription factors that provide a blueprint for segmental identity along the body axis. Recent studies have underscored that in addition to encoding Hox genes, the homeotic clusters contain key noncoding RNA genes that play a central role in development. In this study, we have taken advantage of genome-wide approaches to provide a detailed analysis of retinoic acid (RA)-induced transcriptional and epigenetic changes within the homeotic clusters of mouse embryonic stem cells. Although there is a general colinear response, our analyses suggest a lack of strict colinearity for several genes in the HoxA and HoxB clusters. We have identified transcribed novel noncoding RNAs (ncRNAs) and their cis-regulatory elements that function in response to RA and demonstrated that the expression of these ncRNAs from both strands represent some of the most rapidly induced transcripts in ES cells. Finally, we have provided dynamic analyses of chromatin modifications for the coding and noncoding genes expressed upon activation and suggest that active transcription can occur in the presence of chromatin modifications and machineries associated with repressed transcription state over the clusters. Overall, our data provide a resource for a better understanding of the dynamic nature of the coding and noncoding transcripts and their associated chromatin marks in the regulation of homeotic gene transcription during development.

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“…Owing to the very high conservation of their homeodomain, murine Cdx proteins (Cdx1/2/4) act redundantly in the regulation of their target genes (Savory et al, 2011(Savory et al, , 2009bvan den Akker et al, 2002;van Nes et al, 2006;van Rooijen et al, 2012). Cdx proteins also possess an N-terminal transactivation domain and, accordingly, the vast majority of these target genes are positively regulated (Bansal et al, 2006;Beland et al, 2004;Taylor et al, 1997;Verzi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…However, the importance of this regulation for global trunk NC development in vivo was not evaluated owing to complications typically associated with the study of Cdx null compound mutants (i.e. posterior truncation and/or early embryonic lethality) (Savory et al, 2011(Savory et al, , 2009bvan Rooijen et al, 2012). Via conditional expression of a previously described dominant-negative Cdx protein (Sanchez-Ferras et al, 2012) in the NT and premigratory NCCs, we now show that Cdx proteins play a key early role in the trunk NC GRN, with especially notable implications for subsequent melanocyte development.…”

Section: Introductionmentioning

confidence: 99%

A direct role for murine Cdx proteins in the trunk neural crest-gene regulatory network

et al. 2016

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Numerous studies in chordates and arthropods currently indicate that Cdx proteins have a major ancestral role in the organization of posthead tissues. In urochordate embryos, Cdx loss-of-function has been shown to impair axial elongation, neural tube (NT) closure and pigment cell development. Intriguingly, in contrast to axial elongation and NT closure, a Cdx role in neural crest (NC)-derived melanocyte/ pigment cell development has not been reported in any other chordate species. To address this, we generated a new conditional pan-Cdx functional knockdown mouse model that circumvents Cdx functional redundancy as well as the early embryonic lethality of Cdx mutants. Through directed inhibition in the neuroectoderm, we provide in vivo evidence that murine Cdx proteins impact melanocyte and enteric nervous system development by, at least in part, directly controlling the expression of the key early regulators of NC ontogenesis Pax3, Msx1 and Foxd3. Our work thus reveals a novel role for Cdx proteins at the top of the trunk NC gene regulatory network in the mouse, which appears to have been inherited from their ancestral ortholog.

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Evolutionarily conserved requirement of Cdx for post-occipital tissue emergence

Cited by 62 publications

References 44 publications

Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells

A direct role for murine Cdx proteins in the trunk neural crest-gene regulatory network

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