Roles for FGF8 in the Induction, Initiation, and Maintenance of Chick Limb Development

  title={Roles for FGF8 in the Induction, Initiation, and Maintenance of Chick Limb Development},
  author={Philip H. Crossley and George Minowada and Craig A. MacArthur and Gail Roberta Martin},

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The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor.
Evidence that a member of the fibroblast growth factor (FGF) family emanates from the prospective limb mesoderm to serve as an endogenous initiator for limb bud formation is provided and results suggest that FGF10 is a key mesenchymal factor involved in the initial budding as well as the continuous outgrowth of vertebrate limbs.
FGF7 and FGF10 directly induce the apical ectodermal ridge in chick embryos.
The results suggest that FGF7 and FGF10 directly induce the AER in the ectoderm both of the flank and of the dorsal midline and that these two regions have the competence for AER induction.
Fgf8 is required for outgrowth and patterning of the limbs
It is reported that conditional disruption of Fgf8 in the forelimb of developing mice bypasses embryonic lethality and reveals a requirement for FgF8 inThe formation of the stylopod, anterior zeugopod and autopod.
Initiation of dorso-ventral axis during chick limb development
A role for the mesenchymal T-box gene Brachyury in AER formation during limb development
The results show that T plays a role in the regulation of AER formation, particularly maturation, and suggest that T may also be a component of the epithelialmesenchymal regulatory loop involved in maintenance of a mature functioning AER.
The zebrafish fgf24 mutant identifies an additional level of Fgf signaling involved in vertebrate forelimb initiation
It is shown that the zebrafish fgf24 gene, which belongs to the Fgf8/17/18 subfamily of FgF ligands, acts downstream of tbx5 to activate f gf10 expression in the lateral plate mesoderm, which relays the limb inducing signal to the overlying ectoderm.
Fgf10 is essential for limb and lung formation
It is shown that Fgf10 serves as an essential regulator of lung and limb formation in mice generated with F gf10-deficient mice.
Differential response of Shh expression between chick forelimb and hindlimb buds by FGF‐4
  • N. WadaT. Nohno
  • Biology
    Developmental dynamics : an official publication of the American Association of Anatomists
  • 2001
The difference between the fore and hindlimb buds in the cell competence of Shh induction in response to FGF‐4 is demonstrated, suggesting the possibility that the responsiveness of mesenchymal cells in signaling molecules is not the same in the fore‐ and hind Limb buds.
FGF-stimulated outgrowth and proliferation of limb mesoderm is dependent on syndecan-3.
The outgrowth of the mesoderm of the developing limb bud in response to the apical ectodermal ridge (AER) is mediated at least in part by members of the FGF family. Recent studies have indicated that
Effects of FGFs on the morphogenic potency and AER-maintenance activity of cultured progress zone cells of chick limb bud.
Results indicate that addition of FGF-2 or F GF-4 to cultured PZ cells maintains their competence for Hox gene expression and digit formation, but not their responsiveness to positional cues arising from the zone of polarizing activity (ZPA).


Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse.
Analysis of Fgf-4 expression in the developing mouse embryo suggests that individual members of the gene family are expressed sequentially in developmental pathways such as mesoderm formation and myogenesis, and play a role in specific epithelial-mesenchymal interactions.
FGF-2: apical ectodermal ridge growth signal for chick limb development.
Ectopic fibroblast growth factor (FGF)-2 supplied to the chick apical bud mesoderm after ridge removal will sustain normal gene expression and cell viability, and allow relatively normal limb development.
Mechanisms of limb patterning.
A positive feedback loop coordinates growth and patterning in the vertebrate limb
It is reported here that Fgf4 expression in the ridge can be regulated byshh-expressing cells, and Shh expression in mesenchyme can be activated by FGF4 in combination with retinoic acid, thus establishing a positive feedback loop between ZPA and ridge.