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Gene Review

fgf8a  -  fibroblast growth factor 8a

Danio rerio

Synonyms: SO:0000704, ace, cb110, etID309886.13, fgf-8, ...
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High impact information on fgf8

  • We therefore hypothesized that an excess of Sef eliminates Fgf8 signals and produces an fgf8 null phenotype in ru622 mutants [1].
  • Both the Fgf8 protein and zebrafish "similar expression to fgf genes" protein (Sef), an antagonist of fibroblast growth factors induced by Fgf8 itself, were found to be overexpressed in ru622 mutants [1].
  • Transient misexpression of Lmx1b.1 or Lmx1b.2 during early MMR development induces ectopic wnt1 and fgf8 expression in the MMR, as well as throughout much of the embryo [2].
  • Together, these results demonstrate synergy between oep and fgf8 that operates with regional differences and is involved in the induction, maintenance, movement and survival of mesodermal cell populations [3].
  • The delay in otic induction correlates closely with delayed expression of fgf3 and fgf8 in the hindbrain [4].

Biological context of fgf8

  • Second, combining zygotic mutations in ace/fgf8 and oep disrupts mesoderm formation, a phenotype that is not produced by either mutation alone and is consistent with our model of an interdependence of Fgf8 and Nodal pathways through the genetic regulation of the Nodal co-factor Oep and the cell propagation of Nodal signalling [3].
  • Using gene expression markers for the otic placode, we find that ace/fgf8 and Fgf-signaling are required for normal otic placode formation and maintenance [5].
  • In zebrafish acerebellar (ace) embryos, because of a point mutation in fgf8, the isthmic constriction containing the midbrain-hindbrain boundary (MHB) organizer fails to form [6].
  • Consistent with a requirement for fgf8 function, implantation of FGF8-soaked beads induces fgf17 expression, and expression is upregulated in aussicht mutants, which display upregulation of the Fgf8 signaling pathway [7].

Anatomical context of fgf8

  • Several findings argue that Fgf8 has a direct function in development of cardiac precursor cells: fgf8 is expressed in cardiac precursors and later in the heart ventricle [8].
  • Overexpression of gsk3beta mRNA rescued eyes and the wild-type fgf8 expression of homozygous mbl embryos. emx1 that delineates the telencephalon is expanded and shifted ventroanteriorly in mbl embryos [9].
  • During the development of the zebrafish nervous system both noi, a zebrafish pax2 homolog, and ace, a zebrafish fgf8 homolog, are required for development of the midbrain and cerebellum [10].
  • We propose that, in the developing embryo, localised synthesis of RA by Raldh2 in the anterior psm and in somites activates fgf8 expression which in turn induces the expression of myogenic genes and fast muscle differentiation [11].
  • Attenuated fgf8 signaling results in consistently biased LR asymmetric development of the pharyngeal arches and craniofacial skeleton [12].

Associations of fgf8 with chemical compounds

  • Conversely, treatment of wild-type embryos with retinoic acid greatly expands the periotic domains of expression of fgf3, fgf8, and pax8 and leads to formation of supernumerary and ectopic otic vesicles [13].

Other interactions of fgf8

  • Here we study Erm and Pea3, two ETS domain transcription factors, and show that their expression correlates closely with the domains of fgf8 and fgf3 expression [14].
  • Zebrafish pea3 and erm are general targets of FGF8 signaling [15].
  • In contrast, onset of wnt1, fgf8 and her5 expression occurs normally in the null mutants, but is eliminated later on [16].
  • Our observations suggest that three signaling pathways, involving pax2.1, wnt1 and fgf8, are activated independently in early anterior-posterior patterning of this area [16].
  • Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development [17].

Analytical, diagnostic and therapeutic context of fgf8

  • Using in situ hybridization of early brain marker genes, we found that the most striking effects were an increase in pax2.1 expression in eye stalks associated with absence of either form of PACAP or an increase in eng2 and fgf8 in the midbrain-hindbrain boundary after loss of PACAP2 [18].


  1. Mutation of the atrophin2 gene in the zebrafish disrupts signaling by fibroblast growth factor during development of the inner ear. Asai, Y., Chan, D.K., Starr, C.J., Kappler, J.A., Kollmar, R., Hudspeth, A.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer. O'Hara, F.P., Beck, E., Barr, L.K., Wong, L.L., Kessler, D.S., Riddle, R.D. Development (2005) [Pubmed]
  3. Nodal and Fgf pathways interact through a positive regulatory loop and synergize to maintain mesodermal cell populations. Mathieu, J., Griffin, K., Herbomel, P., Dickmeis, T., Strähle, U., Kimelman, D., Rosa, F.M., Peyriéras, N. Development (2004) [Pubmed]
  4. A direct role for Fgf but not Wnt in otic placode induction. Phillips, B.T., Storch, E.M., Lekven, A.C., Riley, B.B. Development (2004) [Pubmed]
  5. Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear patterning. Léger, S., Brand, M. Mech. Dev. (2002) [Pubmed]
  6. Isthmus-to-midbrain transformation in the absence of midbrain-hindbrain organizer activity. Jászai, J., Reifers, F., Picker, A., Langenberg, T., Brand, M. Development (2003) [Pubmed]
  7. Overlapping and distinct functions provided by fgf17, a new zebrafish member of the Fgf8/17/18 subgroup of Fgfs. Reifers, F., Adams, J., Mason, I.J., Schulte-Merker, S., Brand, M. Mech. Dev. (2000) [Pubmed]
  8. Induction and differentiation of the zebrafish heart requires fibroblast growth factor 8 (fgf8/acerebellar). Reifers, F., Walsh, E.C., Léger, S., Stainier, D.Y., Brand, M. Development (2000) [Pubmed]
  9. Ectopic Wnt signal determines the eyeless phenotype of zebrafish masterblind mutant. van de Water, S., van de Wetering, M., Joore, J., Esseling, J., Bink, R., Clevers, H., Zivkovic, D. Development (2001) [Pubmed]
  10. Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development. Heisenberg, C.P., Brennan, C., Wilson, S.W. Development (1999) [Pubmed]
  11. Retinoic acid activates myogenesis in vivo through Fgf8 signalling. Hamade, A., Deries, M., Begemann, G., Bally-Cuif, L., Genêt, C., Sabatier, F., Bonnieu, A., Cousin, X. Dev. Biol. (2006) [Pubmed]
  12. Roles for fgf8 signaling in left-right patterning of the visceral organs and craniofacial skeleton. Albertson, R.C., Yelick, P.C. Dev. Biol. (2005) [Pubmed]
  13. Zebrafish fgf3 and fgf8 encode redundant functions required for otic placode induction. Phillips, B.T., Bolding, K., Riley, B.B. Dev. Biol. (2001) [Pubmed]
  14. Tight transcriptional control of the ETS domain factors Erm and Pea3 by Fgf signaling during early zebrafish development. Raible, F., Brand, M. Mech. Dev. (2001) [Pubmed]
  15. Zebrafish pea3 and erm are general targets of FGF8 signaling. Roehl, H., Nüsslein-Volhard, C. Curr. Biol. (2001) [Pubmed]
  16. A series of no isthmus (noi) alleles of the zebrafish pax2.1 gene reveals multiple signaling events in development of the midbrain-hindbrain boundary. Lun, K., Brand, M. Development (1998) [Pubmed]
  17. Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development. Draper, B.W., Stock, D.W., Kimmel, C.B. Development (2003) [Pubmed]
  18. Role of two genes encoding PACAP in early brain development in zebrafish. Wu, S., Adams, B.A., Fradinger, E.A., Sherwood, N.M. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
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