Promoter of FGF8 Reveals a Unique Regulation by Unliganded RARα

Brondani, Vincent; Klimkait, Thomas; Egly, Jean‐Marc; Hamy, François

doi:10.1016/s0022-2836(02)00376-5

Cited by 48 publications

(36 citation statements)

References 26 publications

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“…It is established that at many sites in the embryo, RA negatively regulates Fgf signalling (Brondani et al, 2002;Diez del Corral et al, 2003;Zhao et al, 2009). We observed that RA downregulated the Fgf signalling indicator Mkp3, in line with studies in the mouse (Abe et al, 2008;Ryckebusch et al, 2008;Sirbu et al, 2008).…”

Section: Research Articlesupporting

confidence: 90%

“…During the entire period, the topology of tissues and signalling centres changes dramatically. Moreover, evidence is emerging that the various signalling systems regulate each other (Brondani et al, 2002;Park et al, 2008;Ryckebusch et al, 2008;Sirbu et al, 2008;Zhao et al, 2009) (this study). Thus, onset, dynamics and control of head mesoderm patterning is still unclear.…”

Section: Introductionmentioning

confidence: 86%

“…RA, in many settings, promotes cell differentiation (for a review, see Diez del Corral and Storey, 2004); in the head, RA first suppresses cardiac markers to set the posterior limit of the heart field, but then specifies the sinoatrial region of the heart (Hochgreb et al, 2003;Keegan et al, 2005;Ryckebusch et al, 2008;Sirbu et al, 2008). Moreover, RA has the capacity to provide 2819 RESEARCH ARTICLE Head mesoderm patterning cells with a more posterior positional identity (Brondani et al, 2002;Ryckebusch et al, 2008;Sirbu et al, 2008;Zhao et al, 2009). Bmp is a crucial regulator of cardiac development (Schultheiss et al, 1997) and has been suggested to recruit head mesodermal cells into the cardiac lineage (Tirosh-Finkel et al, 2006).…”

Section: Research Articlementioning

confidence: 99%

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Dynamic control of head mesoderm patterning

et al. 2011

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SUMMARYThe embryonic head mesoderm gives rise to cranial muscle and contributes to the skull and heart. Prior to differentiation, the tissue is regionalised by the means of molecular markers. We show that this pattern is established in three discrete phases, all depending on extrinsic cues. Assaying for direct and first-wave indirect responses, we found that the process is controlled by dynamic combinatorial as well as antagonistic action of retinoic acid (RA), Bmp and Fgf signalling. In phase 1, the initial anteroposterior (a-p) subdivision of the head mesoderm is laid down in response to falling RA levels and activation of Fgf signalling. In phase 2, Bmp and Fgf signalling reinforce the a-p boundary and refine anterior marker gene expression. In phase 3, spreading Fgf signalling drives the a-p expansion of MyoR and Tbx1 expression along the pharynx, with RA limiting the expansion of MyoR. This establishes the mature head mesoderm pattern with markers distinguishing between the prospective extra-ocular and jaw skeletal muscles, the branchiomeric muscles and the cells for the outflow tract of the heart.

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Section: Research Articlesupporting

confidence: 90%

Section: Introductionmentioning

confidence: 86%

Section: Research Articlementioning

confidence: 99%

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Dynamic control of head mesoderm patterning

et al. 2011

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“…In prostate cancer cells, RA activation of the Fgf8 promoter produces a switch of splice isoforms, so that a less mitotically active isoform (Fgf8a) accumulates (42). Because both canonical and novel RAresponse elements in the Fgf8 promoter can be activated by unliganded RAR␣ in COS cells (43), an absence of RA may produce an accumulation of the more proliferative Fgf8b product. Hypothetically, the absence of RAR ligand in Raldh2 Ϫ/Ϫ mutants may favor Fgf8b expression, hindering early SHF progenitor differentiation by its increased mitotic activity.…”

Section: Discussionmentioning

confidence: 99%

Retinoic acid deficiency alters second heart field formation

Ryckebüsch

Wang

Bertrand

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

188

240

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Retinoic acid (RA), the active derivative of vitamin A, has been implicated in various steps of cardiovascular development. The retinaldehyde dehydrogenase 2 (RALDH2) enzyme catalyzes the second oxidative step in RA biosynthesis and its loss of function creates a severe embryonic RA deficiency. Raldh2 ؊/؊ knockout embryos fail to undergo heart looping and have impaired atrial and sinus venosus development. To understand the mechanism(s) producing these changes, we examined the contribution of the second heart field (SHF) to pharyngeal mesoderm, atria, and outflow tract in Raldh2 ؊/؊ embryos. RA deficiency alters SHF gene expression in two ways. First, Raldh2 ؊/؊ embryos exhibited a posterior expansion of anterior markers of the SHF, including Tbx1, Fgf8, and the Mlc1v-nlacZ-24/Fgf10 reporter transgene as well as of Islet1. This occurred at early somite stages, when cardiac defects became irreversible in an avian vitamin A-deficiency model, indicating that endogenous RA is required to restrict the SHF posteriorly. Explant studies showed that this expanded progenitor population cannot differentiate properly. Second, RA up-regulated cardiac Bmp expression levels at the looping stage. The contribution of the SHF to both inflow and outflow poles was perturbed under RA deficiency, creating a disorganization of the heart tube. We also investigated genetic cross-talk between Nkx2.5 and RA signaling by generating double mutant mice. Strikingly, Nkx2.5 deficiency was able to rescue molecular defects in the posterior region of the Raldh2 ؊/؊ mutant heart, in a gene dosage-dependent manner.retinoids ͉ retinaldehyde dehydrogenase 2 ͉ heart development ͉ Nkx2.5 ͉ FGF8

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“…Previous studies have shown that RA induces expression of FGF8a isoform while suppressing FGF8b in LNCaP cells (Brondani and Hamy, 2000). The FGF8 promoter contains functional binding sites of RARa, whereas RARa interacts with these DNA binding sites, leading to induction of CAT activity (Brondani et al, 2002). According to the current model of gene regulation by retinoids (Bastien and Rochette-Egly, 2004), unliganded and DNA-bound retinoid receptors repress transcription through the recruitment of corepressors; whereas ligand-induced conformational changes in the receptors cause dissociation of corepressors and recruitment of coactivators (Melnick and Licht, 1999;Aranda and Pascual, 2001;Bastien and Rochette-Egly, 2004).…”

Section: Ra-mediated Rara Hypophosphorylation Induces Fgf8f Expressionmentioning

confidence: 98%