Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways

Li, Nan; Kelsh, Robert N.; Croucher, Peter I.; Roehl, Henry

doi:10.1242/dev.044164

Cited by 38 publications

(36 citation statements)

References 62 publications

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“…During bone development and repair, RA inhibits osteoblast differentiation and drives subsequent matrix synthesis (Laue et al, 2008;Li et al, 2010;Lie and Moren, 2012;Spoorendonk et al, 2008), whereas in the osteoclast lineage, RA signaling has been shown to promote proliferation of precursors and bone matrix resorption but blocks differentiation (Conaway et al, 2009(Conaway et al, , 2013Hu et al, 2010). Our findings on the function of RA signaling in the formation of osteoblasts and osteoclasts during fin regeneration are consistent with those found for bone development and remodeling.…”

Section: Discussionsupporting

confidence: 88%

“…Thus, osteoblasts in the uninjured fin continuously synthesize basal levels of matrix. In larval zebrafish, RA promotes bone matrix synthesis (Laue et al, 2008;Li et al, 2010;Spoorendonk et al, 2008). We therefore expected a comparable role for RA signaling in osteoblasts in the adult fin.…”

Section: Aldh1a2 and Cyp26b1 Cooperate To Control Osteoblast Activitymentioning

confidence: 91%

“…Given the positive role of RA in preosteoblast proliferation, we speculated that RA might keep preosteoblasts in a proliferative state and prevent differentiation towards the distal tip. This notion is also supported by the negative effect of RA signaling on early osteoblastogenesis during zebrafish larval development (Li et al, 2010). To test this hypothesis, we examined preosteoblast differentiation upon RA injection (first IP at 3 dpa).…”

Section: Ra Signaling Prevents Preosteoblast Redifferentiationmentioning

confidence: 94%

“…Retinoic acid (RA) has been shown to play multiple roles in bone development and repair by exerting pleiotropic effects on cells of the chondroblast, osteoblast and osteoclast lineages (Adams et al, 2007;Allen et al, 2002;Conaway et al, 2013;Dranse et al, 2011;Koyama et al, 1999;Laue et al, 2008Laue et al, , 2011Li et al, 2010;Lie and Moren, 2012;Lind et al, 2013;Nallamshetty et al, 2013;Song et al, 2005;Spoorendonk et al, 2008;Weston et al, 2003;Williams et al, 2009). Although partially conflicting results were reported, the general consensus for osteoblastogenesis is that RA signaling restricts osteoblast differentiation but promotes subsequent bone matrix synthesis by mature osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

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Osteoblast de- and redifferentiation is controlled by a dynamic response to retinoic acid during zebrafish fin regeneration

Blum

Begemann

2015

Development

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Zebrafish restore amputated fins by forming tissue-specific blastema cells that coordinately regenerate the lost structures. Fin amputation triggers the synthesis of several diffusible signaling factors that are required for regeneration, raising the question of how cell lineagespecific programs are protected from regenerative crosstalk between neighboring fin tissues. During fin regeneration, osteoblasts revert from a non-cycling, mature state to a cycling, preosteoblastic state to establish a pool of progenitors within the blastema. After several rounds of proliferation, preosteoblasts redifferentiate to produce new bone. Blastema formation and proliferation are driven by the continued synthesis of retinoic acid (RA). Here, we find that osteoblast dedifferentiation and redifferentiation are inhibited by RA signaling, and we uncover how the bone regenerative program is achieved against a background of massive RA synthesis. Stump osteoblasts manage to contribute to the blastema by upregulating expression of the RA-degrading enzyme cyp26b1. Redifferentiation is controlled by a presumptive gradient of RA, in which high RA levels towards the distal tip of the blastema suppress redifferentiation. We show that this might be achieved through a mechanism involving repression of Bmp signaling and promotion of Wnt/β-catenin signaling. In turn, cyp26b1 + fibroblast-derived blastema cells in the more proximal regenerate serve as a sink to reduce RA levels, thereby allowing differentiation of neighboring preosteoblasts. Our findings reveal a mechanism explaining how the osteoblast regenerative program is protected from adverse crosstalk with neighboring fibroblasts that advances our understanding of the regulation of bone repair by RA.

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Section: Discussionsupporting

confidence: 88%

Section: Aldh1a2 and Cyp26b1 Cooperate To Control Osteoblast Activitymentioning

confidence: 91%

Section: Ra Signaling Prevents Preosteoblast Redifferentiationmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Osteoblast de- and redifferentiation is controlled by a dynamic response to retinoic acid during zebrafish fin regeneration

Blum

Begemann

2015

Development

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“…RAR signaling has been studied in some detail in the neural crest (Dupe and Pellerin, 2009;Li et al, 2010;Villanueva et al, 2002); RA is required for eye morphogenesis, otocyst development and specification of the olfactory epithelium (Bok et al, 2011;Lupo et al, 2011;Matt et al, 2005;Radosevic et al, 2011;Rawson and LaMantia, 2006;Romand et al, 2006). Relatively little is known about RAR function in the early patterning of sensory organs of the head.…”

Section: Introductionmentioning

confidence: 99%

RIPPLY3 is a retinoic acid-inducible repressor required for setting the borders of the pre-placodal ectoderm

et al. 2012

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SUMMARYRetinoic acid signaling is a major component of the neural posteriorizing process in vertebrate development. Here, we identify a new role for the retinoic acid receptor (RAR) in the anterior of the embryo, where RAR regulates Fgf8 expression and formation of the pre-placodal ectoderm (PPE). RAR2 signaling induces key pre-placodal genes and establishes the posterolateral borders of the PPE. RAR signaling upregulates two important genes, Tbx1 and Ripply3, during early PPE development. In the absence of RIPPLY3, TBX1 is required for the expression of Fgf8 and hence, PPE formation. In the presence of RIPPLY3, TBX1 acts as a transcriptional repressor, and functions to restrict the positional expression of Fgf8, a key regulator of PPE gene expression. These results establish a novel role for RAR as a regulator of spatial patterning of the PPE through Tbx1 and RIPPLY3. Moreover, we demonstrate that Ripply3, acting downstream of RAR signaling, is a key player in establishing boundaries in the PPE. represses the ability of TBX1 to activate reporter gene constructs in vivo and this inhibition depends on the association of RIPPLY3 with its co-repressor GROUCHO and with TBX1. In agreement with our predictions, RIPPLY3 knockdown perturbs the borders of PPE marker expression. These results demonstrate a novel role for RAR in the precise positioning of the PPE boundaries and establish RIPPLY3 as a key factor that demarcates the boundaries of the PPE. MATERIALS AND METHODS Ripply3 alignment and construction of a phylogenetic treeRipply sequences were obtained from Genbank and Uniprot databases (Benson et al., 2008;Uniprot Consortium, 2009), aligned with MAFFT (L-INS-i algorithm) (Katoh et al., 2009;Katoh et al., 2005) and a phylogenetic tree constructed with PROml, version 3.69 (Protein Maximum Likelihood) (Felsenstein, 2005). Default settings were used, global rearrangements (-G) were performed, and the outgroup (-O) was set to amphioxus. The resultant tree was drawn with FigTree (Rambaut, 2007). Conserved domains of the Ripply gene family were visualized with WebLogo (Crooks et al., 2004;Schneider and Stephens, 1990). EmbryosXenopus eggs were fertilized in vitro as described previously (Blumberg et al., 1997;Koide et al., 2001) and embryos staged according to Nieuwkoop and Faber (Nieuwkoop and Faber, 1967). Embryos were maintained in 0.1ϫ MBS until appropriate stages or treated with 1 M agonist (TTNPB) and 1 M antagonist (AGN193109) as described (Arima et al., 2005). MicroinjectionEmbryos were injected bilaterally or unilaterally at the two-cell stage with combinations of gene specific morpholinos (MO), mRNAs and 100 pg/embryo -galactosidase mRNA lineage tracer. MOs used for this study are found in supplementary material Table S1. Control embryos were injected with 20 ng standard control MO: CCT CTT ACC TCA GTT ACA ATT TAT A (GeneTools). The following plasmids were constructed by PCR amplification of the protein-coding regions of the indicated genes and cloning into the expression vector pCDG1: xRARa2.2 (Sharpe, ...

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Developmental toxicity screening in zebrafish

McCollum

Ducharme

Bondesson

et al. 2011

Birth Defects Research Part C: Embryo Today: Reviews

140

101

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Given the ever-increasing toxic exposure ubiquitously present in our environment as well as emerging evidence that these exposures are hazardous to human health, the current rodent-based regulations are proving inadequate. In the process of overhauling risk assessment methodology, a nonrodent test organism, the zebrafish, is emerging as tractable for medium- and high-throughput assessments, which may help to accelerate the restructuring of standards. Zebrafish have high developmental similarity to mammals in most aspects of embryo development, including early embryonic processes, and on cardiovascular, somite, muscular, skeletal, and neuronal systems. Here, we briefly describe the development of these systems and then chronicle the toxic impacts assessed following chemical exposure. We also compare the available data in zebrafish toxicity assays with two databases containing mammalian toxicity data. Finally, we identify gaps in our collective knowledge that are ripe for future studies.

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Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways

Cited by 38 publications

References 62 publications

Osteoblast de- and redifferentiation is controlled by a dynamic response to retinoic acid during zebrafish fin regeneration

Osteoblast de- and redifferentiation is controlled by a dynamic response to retinoic acid during zebrafish fin regeneration

RIPPLY3 is a retinoic acid-inducible repressor required for setting the borders of the pre-placodal ectoderm

Developmental toxicity screening in zebrafish

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