The Mouse Cer1 (Cerberus related or homologue) Gene Is Not Required for Anterior Pattern Formation

Simpson, Eleanor H.; Johnson, Dabney K.; Hunsicker, Patricia R.; Suffolk, Ruth; Jordan, Siobhán A.; Jackson, Ian J.

doi:10.1006/dbio.1999.9372

Cited by 54 publications

(26 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this model has not been demonstrated conclusively by loss-of-function analysis (Simpson et al 1999;Belo et al 2000;Shawlot et al 2000). When cerberus mRNA is microinjected into early Xenopus embryos, ectopic heads (as marked by eye and cement gland) are formed in ∼36% of the embryos (Fig.…”

Section: Rar and Head Induction By Cerberusmentioning

confidence: 99%

Active repression of RAR signaling is required for head formation

Koide¹,

Downes²,

et al. 2001

View full text Add to dashboard Cite

The retinoic acid receptors (RARs) recruit coactivator and corepressor proteins to activate or repress the transcription of target genes depending on the presence of retinoic acid (RA). Despite a detailed molecular understanding of how corepressor complexes function, there is no in vivo evidence to support a necessary function for RAR-mediated repression. Signaling through RARs is required for patterning along the anteroposterior (A-P) axis, particularly in the hindbrain and posterior, although the absence of RA is required for correct anterior patterning. Because RARs and corepressors are present in regions in which RA is absent, we hypothesized that repression mediated through unliganded RARs might be important for anterior patterning. To test this hypothesis, specific reagents were used that either reduce or augment RAR-mediated repression. Derepression of RAR signaling by expressing a dominant-negative corepressor resulted in embryos that exhibited phenotypes similar to those treated by RA. Anterior structures such as forebrain and cement gland were greatly reduced, as was the expression of molecular markers. Enhancement of target gene repression using an RAR inverse agonist resulted in up-regulation of anterior neural markers and expansion of anterior structures. Morpholino antisense oligonucleotide-mediated RAR␣ loss-of-function phenocopied the effects of RA treatment and dominant-negative corepressor expression. Microinjection of wild-type or dominant-negative RAR␣ rescued the morpholino phenotype, confirming that RAR is functioning anteriorly as a transcriptional repressor. Lastly, increasing RAR-mediated repression potentiated head-inducing activity of the growth factor inhibitor cerberus, whereas releasing RAR-mediated repression blocked cerberus from inducing ectopic heads. We conclude that RAR-mediated repression of target genes is critical for head formation. This requirement establishes an important biological role for active repression of target genes by nuclear hormone receptors and illustrates a novel function for RARs during vertebrate development.

show abstract

Section: Rar and Head Induction By Cerberusmentioning

confidence: 99%

Active repression of RAR signaling is required for head formation

Koide¹,

Downes²,

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Unlike its Xenopus counterpart, mouse Cerl-1 does not bind Wnt and inhibit Wnt signaling (Belo et al 2000) and is not essential for mouse head formation (Table 1) (Simpson et al 1999;Belo et al 2000;Shawlot et al 2000;Stanley et al 2000). Rather, Cerberus-related proteins are key regulators of Nodal signaling and play an important role in the establishment of left -right asymmetry in the vertebrate embryo (Rodriguez Esteban et al 1999;Yokouchi et al 1999;Zhu et al 1999;Hashimoto et al 2004;Marques et al 2004;Tavares et al 2007;Vonica and Brivanlou 2007).…”

Section: Cerberusmentioning

confidence: 99%

Secreted and Transmembrane Wnt Inhibitors and Activators

Cruciat

Niehrs

2012

Cold Spring Harbor Perspectives in Biology

532

450

View full text Add to dashboard Cite

“…We found that Cerberus is not induced by Wnt antagonists, but others have shown it and mouse Cerberus-like to be up-regulated by Nodal (Ding et al 1998;Brennan et al 2001;Norris et al 2002;Yamamoto et al 2003). Although mouse Cerberus-like differs importantly from Xenopus Cerberus in its inability to bind Wnt (Belo et al 2000), functional overlap between Hex and Cerberus or Cerberus-like might reinforce heart induction in Xenopus but constitute sufficient redundancy to cause only structural malformations in Hex mutant mice and perhaps contribute to absence of a heart phenotype in Cerberus-like mutants (Simpson et al 1999;Belo et al 2000;Shawlot et al 2000).…”

Section: Hex In the Context Of Heart-inducing Pathwaysmentioning

confidence: 99%

Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex

Foley¹,

Mercola²

2005

Genes Dev.

181

163

View full text Add to dashboard Cite

Inhibition of canonical Wnt/␤-catenin signaling by Dickkopf-1 (Dkk-1) or Crescent initiates cardiogenesis in vertebrate embryos. However, nearly nothing is known about the downstream effectors of these secreted Wnt antagonists or the mechanism by which they activate heart formation. Here we show that Wnt antagonists in Xenopus stimulate cardiogenesis non-cell-autonomously, up to several cells away from those in which canonical Wnt/␤-catenin signaling is blocked, indicative of an indirect role in heart induction. A screen for downstream mediators revealed that Dkk-1 and other inhibitors of the canonical Wnt pathway induce the homeodomain transcription factor Hex, which is normally expressed in endoderm underlying the presumptive cardiac mesoderm in amphibian, bird, and mammalian embryos. Loss of Hex function blocks both endogenous heart development and ectopic heart induction by Dkk-1. As with the canonical Wnt pathway antagonists, ectopic Hex induces expression of cardiac markers non-cell-autonomously. Thus, to initiate cardiogenesis, Wnt antagonists act on endoderm to up-regulate Hex, which, in turn, controls production of a diffusible heart-inducing factor. This novel function for Hex suggests an etiology for the cardiac malformations in Hex mutant mice and will make possible the isolation of factors that induce heart directly in the mesoderm.

show abstract

The Mouse Cer1 (Cerberus related or homologue) Gene Is Not Required for Anterior Pattern Formation

Cited by 54 publications

References 28 publications

Active repression of RAR signaling is required for head formation

Active repression of RAR signaling is required for head formation

Secreted and Transmembrane Wnt Inhibitors and Activators

Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex

Contact Info

Product

Resources

About