Zebrafish fgf24functions withfgf8to promote posterior mesodermal development

Abstract

Fibroblast growth factor (Fgf) signaling plays an important role during development of posterior mesoderm in vertebrate embryos. Blocking Fgf signaling by expressing a dominant-negative Fgf receptor inhibits posterior mesoderm development. In mice, Fgf8 appears to be the principal ligand required for mesodermal development, as mouse Fgf8 mutants do not form mesoderm. In zebrafish, Fgf8 is encoded by the acerebellarlocus, and, similar to its mouse otholog, is expressed in early mesodermal precursors during gastrulation. However, zebrafish fgf8 mutants have only mild defects in posterior mesodermal development, suggesting that it is not the only Fgf ligand involved in the development of this tissue. We report here the identification of an fgf8-related gene in zebrafish, fgf24, that is co-expressed with fgf8 in mesodermal precursors during gastrulation. Using morpholino-based gene inactivation, we have analyzed the function of fgf24 during development. We found that inhibiting fgf24 function alone has no affect on the formation of posterior mesoderm. Conversely, inhibiting fgf24 function in embryos mutant for fgf8 blocks the formation of most posterior mesoderm. Thus, fgf8 and fgf24 are together required to promote posterior mesodermal development. We provide both phenotypic and genetic evidence that these Fgf signaling components interact with no tailand spadetail, two zebrafish T-box transcription factors that are required for the development of all posterior mesoderm. Last, we show that fgf24 is expressed in early fin bud mesenchyme and that inhibiting fgf24 function results in viable fish that lack pectoral fins.

Duplication and divergence of fgf8 functions in teleost development and evolution

“…As in mouse only Fgf4, Fgf8, Fgf9, and Fgf17 are known to be expressed in the AER (Niswander and Martin,'92;Heikinheimo et al,'94;Ohuchi et al,'94;Crossley and Martin,'95;Mahmood et al,'95), this suggests complex regulatory evolution and either the loss of function of Fgf16 in tetrapod limb development or the acquisition of fgf16 function in pectoral fin formation in ray-fin fish. Regardless of the exact evolutionary scenario, our results and those mentioned above (Reifers et al, '98;Draper et al, 2003;Fischer et al, 2003;Nomura et al, 2006) show that mechanisms of vertebrate limb development are less conserved than previously thought. More generally, these results call into question conclusions regarding the universality of gene function and developmental processes drawn from a few model organisms and point to the need to expand developmental studies beyond model clades and to interpret results in an evolutionary context.…”

A gene regulatory network directed by zebrafish No tail accounts for its roles in mesoderm formation

“…1B). At least 11 of these genes have been previously reported to be downregulated in ntl mutant embryos (8,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and we highlight below several other genes whose expression is genetically regulated by Ntl.…”

“…sp5l is also a target of FGF signaling and itself regulates ntl expression (35). We have also included in the GRN other transcription factors that are involved in posterior patterning and are bound and regulated by Ntl and/or Wnt signaling: cdx1a, cdx4, and eve1 and fgf8, which works in combination with fgf24 in the posterior of the embryo (13,36). Tbx16 also regulates the expression of some of these targets, revealing another feed-forward loop, and we have indicated these interactions in Fig.…”

Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity

“…6 We hypothesize that FBLN1 might be affecting FGF8 at the level of sonic hedgehog as well as a direct interaction to maintain its presence and availability for NCC survival. Although there is a high degree of redundancy in FGF protein family signaling, it appears that the interaction of FBLN1 and FGF8 is not compensated by other members of the FGF family (mainly FGF3 (32) and FGF24 (33)) to rescue the double heterozygote embryos. Moreover, the interaction of FBLN1 6 W. O. Twal, unpublished data.…”