Skip to main content

Advertisement

SpringerLink
Log in

Zebrafish fgfr1 is a member of the fgf8 synexpression group and is required for fgf8 signalling at the midbrain-hindbrain boundary

  • Original Article
  • Published:
Development Genes and Evolution Aims and scope Submit manuscript

Abstract

FGFR1 is an important signalling molecule during embryogenesis and in adulthood. FGFR1 mutations in human may lead to developmental defects and pathological conditions, including cancer and Alzheimer’s disease. Here, we describe cloning and expression analysis of the zebrafish fibroblast growth factor receptor 1 (fgfr1). Initially, fgfr1 is expressed in the adaxial mesoderm with transcripts distinctly localised to the anterior portion of each half-somite. Hereupon, fgfr1 is also strongly expressed in the otic vesicles, branchial arches and the brain, especially at the midbrain-hindbrain boundary (MHB). The expression patterns of fgfr1 and fgf8 are strikingly similar and knock-down of fgfr1 phenocopies many aspects observed in the fgf8 mutant acerebellar, suggesting that Fgf8 exerts its function mainly by binding to FgfR1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2a–d
Fig. 3a–m
Fig. 4a–h
Fig. 5a–h

Similar content being viewed by others

References

  • Amaya E, Stein PA, Musci TJ, Kirschner MW (1993) FGF signalling in the early specification of mesoderm in Xenopus. Development 118:477–487

    CAS  PubMed  Google Scholar 

  • Brand M, Heisenberg CP, Jiang YJ, Beuchle D, Lun K, Furutani-Seiki M, Granato M, Haffter P, Hammerschmidt M, Kane DA, Kelsh RN, Mullins MC, Odenthal J, van Eeden FJ, Nusslein-Volhard C (1996) Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain. Development 123:179–190

    CAS  PubMed  Google Scholar 

  • Burgar HR, Burns HD, Elsden JL, Lalioti MD, Heath JK (2002) Association of the signalling adaptor FRS2 with fibroblast growth factor receptor 1 (Fgfr1) is mediated by alternative splicing of the juxtamembrane domain. J Biol Chem 277:4018–4023

    Article  CAS  PubMed  Google Scholar 

  • Chi CL, Martinez S, Wurst W, Martin GR (2003) The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development 130:2633–2644

    Article  CAS  PubMed  Google Scholar 

  • Ciruna B, Rossant J (2001) FGF signaling regulates mesoderm cell fate specification and morphogenetic movements at the primitive streak. Dev Cell 1(1):37–49

    Article  CAS  PubMed  Google Scholar 

  • Cote GJ, Huang ESC, Jin W, Morrison RS (1997) Sequence requirements for regulated RNA splicing of the human fibroblast growth factor receptor-1 a exon. J Biol Chem 272:1054–1060

    Article  CAS  PubMed  Google Scholar 

  • Deng CX, Wynshaw-Boris A, Shen MM, Daugherty C, Ornitz DM, Leder P (1994) Murine FGFR-1 is required for early postimplantation growth and axial organization. Genes Dev 8:3045–3057

    CAS  PubMed  Google Scholar 

  • Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss MR, Burgess WH, Jaye M, Schlessinger J (1990) Cloning of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. EMBO J 9:2685–2692

    CAS  PubMed  Google Scholar 

  • Felsenstein J (1989) PHYLIP—phylogeny interference package. Cladistics 5:164–166

    Google Scholar 

  • Fürthauer M, Thisse C, Thisse B (1997) A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula. Development 124:4253–4264

    PubMed  Google Scholar 

  • Fürthauer M, Reifers F, Brand M, Thisse B, Thisse C (2001) sprouty4 acts in vivo as a feed-back-induced antagonist of FGF signalling in zebrafish. Development 128:2175–2186

    CAS  PubMed  Google Scholar 

  • Fürthauer M, Lin W, Ang SL, Thisse B, Thisse C (2002) Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling. Nat Cell Biol 4:170–174

    Article  PubMed  Google Scholar 

  • Gillespie LL, Chen G, Paterno GD (1995) Cloning of a fibroblast growth factor receptor 1 splice variant from Xenopus embryos that lacks a protein kinase C site important for the regulation of receptor activity. J Biol Chem 270:22758–22763

    Article  CAS  PubMed  Google Scholar 

  • Givol D, Yayon A (1992) Complexity of FGF receptors: genetic basis for structural diversity and functional specificity. FASEB J 6:3362–3369

    CAS  PubMed  Google Scholar 

  • Golub R, Adelman Z, Clementi J, Weiss R, Bonasera J, Servetnick M (2000) Evolutionary conserved and divergent expression of the FGF receptor family among vertebrate embryos, as revealed by FGFR expression patterns in Xenopus. Dev Genes Evol 210:345–357

    Article  CAS  PubMed  Google Scholar 

  • Groth C, Lardelli M (2002) The structure and function of vertebrate fibroblast growth factor receptor 1. Int J Dev Biol 46:393–400

    CAS  PubMed  Google Scholar 

  • Heikinheimo M, Lawshe A, Shackleford GM, Wilson DB, MacArthur CA (1994) Fgf-8 expression in the post-gastrulation mouse suggests roles in the development of the face, limbs and central nervous system. Mech Dev 48:129–138

    Article  CAS  PubMed  Google Scholar 

  • Hukriede NA, Joly L, Tsang M, Miles J, Tellis P, Epstein JA, Barbazyk WA, Li FN, Paw B, Postlethwait JH, Hudson TJ, Zon LI, McPherson JD, Chevrette M, Dawid IB, Johnson SL, Ekker M (1999) Radiation hybrid mapping of the zebrafish genome. Proc Natl Acad Sci USA 96:9745–9750

    Article  CAS  PubMed  Google Scholar 

  • Irving C, Mason I (2000) Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression. Development 127(1):177–186

    CAS  PubMed  Google Scholar 

  • Jaszai J, Reifers F, Picker A, Langenberg T, Brand M (2003) Isthmus-to-midbrain transformation in the absence of midbrain-hindbrain organizer activity. Development 130:6611–6623

    Article  CAS  PubMed  Google Scholar 

  • Johnson DE, Williams LT (1993) Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res 60:1–41

    CAS  PubMed  Google Scholar 

  • Johnson DE, Lu J, Chen H, Werner S, Williams LT (1991) The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain. Mol Cell Biol 11:4627–4634

    CAS  PubMed  Google Scholar 

  • Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203:253–310

    CAS  PubMed  Google Scholar 

  • Lardelli M (1997) Generation and PCR screening of bacteriophage lambda sublibraries enriched for rare clones (the “sublibrary method”). In: White BA (ed) PCR cloning protocols: from molecular cloning to genetic engineering. Totowa Methods Mol Biol 67:345–355

    CAS  Google Scholar 

  • Leger S, Brand M (2002) Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear pattering. Mech Dev 119:91–108

    Article  CAS  PubMed  Google Scholar 

  • Liu A, Joyner AL (2001) EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development 128(2):181–191

    CAS  PubMed  Google Scholar 

  • Lun K, Brand M (1998) A series of no isthmus (noi) alleles of the zebrafish pax2.1 reveals multiple signaling events in development of the midbrain-hindbrain boundary. Development 125:3049–3062

    CAS  PubMed  Google Scholar 

  • Mahmood R, Bresnick J, Hornbruch A, Mahony C, Morton N, Colquhoun K, Martin P, Lumsden A, Dickson C, Mason I (1995) A role for FGF-8 in the initiation and maintenance of vertebrate limb bud outgrowth. Curr Biol 5:797–806

    CAS  PubMed  Google Scholar 

  • Nasevicius A, Ekker SC (2000) Effective targeted gene ‘knockdown’ in zebrafish. Nat Genet 26:216–220

    Article  CAS  PubMed  Google Scholar 

  • Ornitz DM, Itoh N (2001) Fibroblast growth factors. Genome Biol 2:1–12

    Article  Google Scholar 

  • Partanen J, Schwartz L, Rossant J (1998) Opposite phenotypes of hypomorphic and Y766 phosphorylation site mutations reveal a function for Fgfr1 in anteroposterior patterning of mouse embryos. Genes Dev 12:2332–2344

    CAS  PubMed  Google Scholar 

  • Passos-Bueno MR, Wilcox WR, Jabs EW, Sertie AL, Alonso LG, Kitoh H (1999) Clinical spectrum of fibroblast growth factor receptor mutations. Hum Mutat 14:115–125

    CAS  PubMed  Google Scholar 

  • Paterno GD, Ryan PJ, Kao KR, Gillespie LL (2000) The VT+ and VT− isoforms of the fibroblast growth factor receptor type 1 are differentially expressed in the presumptive mesoderm of Xenopus embryos and differ in their ability to mediate mesoderm formation. J Biol Chem 275:9581–9586

    Article  CAS  PubMed  Google Scholar 

  • Peters KG, Werner S, Chen G, Williams LT (1992) Two FGF receptor genes are differently expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. Development 114:233–243

    CAS  PubMed  Google Scholar 

  • Picker A, Brennan C, Reifers F, Böhli H, Holder N, Brand M (1999) Requirement for zebrafish acerebellar/FGF8 in midbrain polarization, mapping and confinement of the retinotectal projection. Development 126:2967–2978

    CAS  PubMed  Google Scholar 

  • Raible F, Brand M (2001) Tight transcriptional control of the ETS domain factors Erm and Pea3 by Fgf signaling during early zebrafish development. Mech Dev 107:105–117

    Article  CAS  PubMed  Google Scholar 

  • Reifers F, Böhli H, Walsh EC, Crossley PH, Stanier DYR, Brand M (1998) Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis. Development 125:2381–2395

    CAS  PubMed  Google Scholar 

  • Roehl H, Nüsslein-Volhard C (2001) Zebrafish pea3 and erm are general targets of FGF8 signaling. Curr Biol 11:503–507

    Article  CAS  PubMed  Google Scholar 

  • Rupp AW, Snider L, Weintraub H (1994) Xenopus embryos regulate the nuclear localization of XMyoD. Genes Dev 8:1311–1323

    CAS  PubMed  Google Scholar 

  • Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225

    CAS  PubMed  Google Scholar 

  • Scholpp S, Lohs C, Brand M (2003) Engrailed and Fgf8 act synergistically to maintain the boundary between diencephalon and mesencephalon. Development 130:4881–4893

    Article  CAS  PubMed  Google Scholar 

  • Slepsova-Friedrich I, Li Y, Emelyanov A, Ekker M, Korzh V, Ge R (2001) fgfr3 and regionalization of anterior neural tube in zebrafish. Mech Dev 102:213–217

    Article  PubMed  Google Scholar 

  • Sun X, Meyers EN, Lewandoski M, Martin GR (1999) Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo. Genes Dev 13:1834–1846

    CAS  PubMed  Google Scholar 

  • Szebenyi G, Fallon JF (1999) Fibroblast growth factors as multifunctional signaling factors. Int Rev Cytol 185:45–106

    CAS  PubMed  Google Scholar 

  • Takami K, Matsuo A, Terai K, Walker DG, McGeer EG, McGeer PL (1998) Fibroblast growth factor receptor-1 expression in the cortex and hippocampus in Alzheimer’s disease. Brain Res 802:89–97

    Article  CAS  PubMed  Google Scholar 

  • Tamme R, Mills K, Rainbird B, Nornes S, Lardelli M (2001) Simple, directional cDNA cloning for in situ transcript hybridisation screens. BioTechniques 31:938–946

    CAS  PubMed  Google Scholar 

  • Thisse B, Thisse C, Weston JA (1995) Novel FGF receptor (Z-FGFR4) is dynamically expressed in mesoderm and neuroectoderm during early zebrafish embryogenesis. Dev Dyn 203:377–391

    CAS  PubMed  Google Scholar 

  • Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680

    PubMed  Google Scholar 

  • Trokovic R, Trokovic N, Hernesniemi S, Pirvola U, Vogt Weisenhorn DM, Rossant J, McMahon AP, Wurst W, Partanen J (2003) FGFR1 is independently required in both developing mid- and hindbrain for sustained response to isthmic signals. EMBO J 22:1811–1823

    Article  CAS  PubMed  Google Scholar 

  • Tsang M, Friesel R, Kudoh T, Dawid IB (2002) Identification of Sef, a novel modulator of FGF signalling. Nat Cell Biol 4:165–169

    Article  CAS  PubMed  Google Scholar 

  • Valve EM, Nevalainen MT, Nurmi MJ, Laato MK, Martikainen PM, Harkonen PL (2001) Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia lesions and prostate cancer. Lab Invest 81:815–826

    CAS  PubMed  Google Scholar 

  • Walshe J, Mason I (2000) Expression of FGFR1, FGFR2 and FGFR3 during early neural development in the chick embryo. Mech Dev 90:103–110

    Article  CAS  PubMed  Google Scholar 

  • Yamaguchi TP, Conlon RA, Rossant J (1992) Expression of the fibroblast growth factor receptor FGFR-1/flg during gastrulation and segmentation in the mouse embryo. Dev Biol 152:75–88

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Clemens Kiecker for comments on the manuscript. Casper Groth was supported by an International Postgraduate Research Scholarship from the University of Adelaide and by funds from the Danish Research Agency. Michael Lardelli is supported by funds from the Australian Research Council via the Centre for the Molecular Genetics of Development. Steffen Scholpp, Claudia Lohs and Michael Brand were supported through grants by the European Union (QLG3-CT- 2001-02310), the Deutsche Forschungsgemeinschaft, and the Max-Planck-Society.

Author information

Author notes

  1. Steffen Scholpp

    Present address: MRC Centre for Developmental Neurobiology, New Hunt’s House, Guy’s Campus, London, SE1 1UL, UK

  2. Casper Groth

    Present address: Department of Biological Sciences, Vanderbilt University, VU Station B, Box 35-1634, Nashville, TN, 37235-1634, USA

Authors and Affiliations

  1. Max-Planck Institute of Molecular Cell Biology and Genetics, Department of Genetics, University of Technology (TU), 01307, Dresden, Germany

    Steffen Scholpp, Claudia Lohs & Michael Brand

  2. School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, SA, 5005, Australia

    Casper Groth & Michael Lardelli

Authors
  1. Steffen Scholpp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Casper Groth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claudia Lohs
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Lardelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Brand
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Brand.

Additional information

Steffen Scholpp and Casper Groth contributed equally to this work.

Edited by D. Tautz

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scholpp, S., Groth, C., Lohs, C. et al. Zebrafish fgfr1 is a member of the fgf8 synexpression group and is required for fgf8 signalling at the midbrain-hindbrain boundary. Dev Genes Evol 214, 285–295 (2004). https://doi.org/10.1007/s00427-004-0409-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00427-004-0409-1

Keywords

Search

Navigation