FGF receptor gene expression and its regulation by FGF signaling during early zebrafish development

Ota, Satoshi; Tonou-Fujimori, Noriko; Nakayama, Yukiko; Ito, Yuki; Kawamura, Akinori; Yamasu, Kyo

doi:10.1002/dvg.20682

Cited by 31 publications

(32 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since ethanol suppressed miR-9, we predicted that target mRNAs would be induced following ethanol exposure. We assessed the expression of three important developmental genes, FOXP2, FGFR-1 and MECP2 (Haesler et al, 2004; Hendrich and Tweedie, 2003; Ota et al, 2010; Riley et al, 2007; Shu et al, 2007). FOXP 2 is predicted to be a strong, vertebrate-conserved target of miR-9, with two 7mer-m8 sites in the proximate 3′UTR (www.targetscan.org), while FGFR-1 has been shown to be a miR-9 target in the zebrafish (Leucht et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…For quantification of the premature miRNAs (pre-miR-9-1, pre-miR-9-2, and pre-miR-9-3), cDNA was synthesized using qScript cDNA supermix reverse transcription reaction according to manufacturer’s protocol, at an average concentration of 12.5ng RNA/μL total cDNA (Quanta Biosciences, Gaithersburg, MD). We also assessed the expression of three mRNAs that are highly expressed during embryogenesis across species (Hendrich and Tweedie, 2003; Ota et al, 2010; Shu et al, 2007) and are implicated in pervasive developmental disorders in humans (Allan et al, 2008; Haesler et al, 2004; Hagberg, 2002; Poot et al, 2009; Riley et al, 2007). These include a previously identified miR-9 target FGFR- 1 (Leucht et al, 2008; Rodriguez-Otero et al, 2011), a predicted vertebrate conserved miR-9 target, FOXP2 (www.targetscan.org), and an mRNA not predicted to be targeted by miR-9 in either mouse or zebrafish, MECP2.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Suppression and Epigenetic Regulation of MiR‐9 Contributes to Ethanol Teratology: Evidence from Zebrafish and Murine Fetal Neural Stem Cell Models

Pappalardo-Carter

Balaraman

Sathyan

et al. 2013

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

Background Fetal alcohol exposure produces multi-organ defects, making it difficult to identify underlying etiological mechanisms. However, recent evidence for ethanol sensitivity of the miRNA miR-9, suggests one mechanism whereby ethanol broadly influences development. We hypothesized that loss of miR-9 function recapitulates aspects of ethanol teratology. Methods Zebrafish embryos were exposed to ethanol during gastrulation, or injected with anti-miR-9 or nonsense control morpholinos during the 2-cell stage of development and collected between 24 and 72 hours post fertilization (hpf). We also assessed the expression of developmentally important, and known miR-9 targets, FGFR-1, FOXP2, and the non-targeted transcript, MECP2. Methylation at CpG islands of mammalian miR-9 genes was assessed in fetal murine neural stem cells (mNSCs) by methylation-specific PCR, and miRNA processing assessed by qRT-PCR for pre-miR-9 transcripts. Results Ethanol treatment and miR-9 knockdown resulted in similar cranial defects including microcephaly. Additionally, ethanol transiently suppressed miR-9, as well as FGFR-1 and FOXP2, and alterations in miR-9 expression were correlated with severity of ethanol-induced teratology. In mNSCs, ethanol increased CpG dinucleotide methylation at the miR-9-2 locus and accumulation of pre-miR-9-3. Conclusions Ethanol exerts regulatory control at multiple levels of miR-9 biogenesis. Moreover, early embryonic loss of miR-9 function recapitulated the severe range of teratology associated with developmental ethanol exposure. Ethanol also disrupts the relationship between miR-9 and target gene expression, suggesting a nuanced relationship between ethanol and miRNA regulatory networks in the developing embryo. The implications of these data for the expression and function of mature miR-9 warrant further investigation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Suppression and Epigenetic Regulation of MiR‐9 Contributes to Ethanol Teratology: Evidence from Zebrafish and Murine Fetal Neural Stem Cell Models

Pappalardo-Carter

Balaraman

Sathyan

et al. 2013

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

show abstract

“…Although not differentially expressed, fgfr1a and fgfr1b are both are expressed in all or almost all cells during cleavage stages up to early gastrulation. After this, expression becomes more restricted, but persists in the anterior neural plate during gastrulation (Ota et al, 2010; Ota et al, 2009; Rohner et al, 2009; Thisse et al, 2001). These data are consistent with fgf8a, fgf17, fgfr1a, and fgfr1b being part of the pathway that mediates mesendoderm/mesoderm to neuroectoderm communication or acting within the neuroectoderm to promote anterior neurulation.…”

Section: Discussionmentioning

confidence: 99%

Identification of transcripts potentially involved in neural tube closure using RNA sequencing

Kindt

Perosino

Ersfeld

et al. 2018

Genesis

View full text Add to dashboard Cite

Anencephaly is a fatal human neural tube defect (NTD) in which the anterior neural tube remains open. Zebrafish embryos with reduced Nodal signaling display an open anterior neural tube phenotype that is analogous to anencephaly. Previous work from our laboratory suggests that Nodal signaling acts through induction of the head mesendoderm and mesoderm. Head mesendoderm/mesoderm then, through an unknown mechanism, promotes formation of the polarized neuroepithelium that is capable of undergoing the movements required for closure. We compared the transcriptome of embryos treated with a Nodal signaling inhibitor at sphere stage, which causes NTDs, to embryos treated at 30% epiboly, which does not cause NTDs. This screen identified over 3,000 transcripts with potential roles in anterior neurulation. Expression of several genes encoding components of tight and adherens junctions was significantly reduced, supporting the model that Nodal signaling regulates formation of the neuroepithelium. mRNAs involved in Wnt, FGF, and BMP signaling were also differentially expressed, suggesting these pathways might regulate anterior neurulation. In support of this, we found that pharmacological inhibition of FGF-receptor function causes an open anterior NTD as well as loss of mesodermal derivatives. This suggests that Nodal and FGF signaling both promote anterior neurulation through induction of head mesoderm.

show abstract

“…Among them, immunoglobulin-like domain ΙΙΙ is involved in the determination of ligand-binding specificity and Fgfr1 - Fgfr3 encode two major versions of the domain (ΙΙΙb and ΙΙΙc) generated by alternative splicing (Itoh and Ornitz, 2004). Human FGF22 specifically bound to human FGFR2b in vitro and zebrafish fgfr2 are expressed in the midbrain during somitogenesis (Zhang et al, 2006; Ota et al, 2010). These findings suggest fgfr2b to be involved in the roles of fgf22 in the midbrain; therefore, we injected two splice-site-targeted MOs (MO1 and MO2) for fgfr2b into 2-cell embryos to investigate the role of fgfr2b in midbrain development.…”

Section: Resultsmentioning

confidence: 99%

Fgf22 regulated by Fgf3/Fgf8 signaling is required for zebrafish midbrain development

Miyake

Itoh

2013

Biology Open

View full text Add to dashboard Cite

SummaryFibroblast growth factor (Fgf) signaling plays important roles in various developmental processes including brain development. Here, we identified zebrafish fgf22 predominantly expressed in the posterior midbrain and anterior midbrain–hindbrain boundary (MHB) primordia during early embryonic brain development. To examine roles of Fgf22 in midbrain development, we analyzed fgf22 knockdown embryos. The fgf22 morphants were defective in proper formation of the MHB constriction and the midbrain. The knockdown of fgf22 caused decreased cell proliferation in the midbrain, expanded expression of roof plate and tegmental marker genes, and decreased expression of tectal marker genes, indicating that Fgf22 is required for cell proliferation, roof plate formation, and tectum specification in the midbrain. Fgf receptor 2b (Fgfr2b), a potential receptor for Fgf22, was also required, indicating that Fgf22 signaling is mediated through Fgfr2b. The floor plate and the MHB are crucial for the dorsoventral patterning of the midbrain through Hedgehog (Hh) and Fgf signaling, respectively. The fgf3/fgf8 double morphant phenotype was essentially similar to that of fgf22 morphants, whereas the phenotype caused by inhibition of Hh signaling was not. fgf3 and fgf8 were expressed earlier than fgf22 in the MHB primordium and Fgf3/Fgf8 signaling was required for fgf22 expression in the posterior midbrain. Furthermore, fgf22 partially rescued the fgf3/fgf8 double morphant phenotype. The present results indicate Fgf22 to be involved in midbrain development downstream of Fgf3 and Fgf8 in the MHB but not of Hh in the floor plate.

show abstract

FGF receptor gene expression and its regulation by FGF signaling during early zebrafish development

Cited by 31 publications

References 54 publications

Suppression and Epigenetic Regulation of MiR‐9 Contributes to Ethanol Teratology: Evidence from Zebrafish and Murine Fetal Neural Stem Cell Models

Suppression and Epigenetic Regulation of MiR‐9 Contributes to Ethanol Teratology: Evidence from Zebrafish and Murine Fetal Neural Stem Cell Models

Identification of transcripts potentially involved in neural tube closure using RNA sequencing

Fgf22 regulated by Fgf3/Fgf8 signaling is required for zebrafish midbrain development

Contact Info

Product

Resources

About