Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development - PubMed (original) (raw)
Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development
X Sun et al. Nat Genet. 2000 May.
Abstract
Development of the vertebrate limb bud depends on reciprocal interactions between the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER). Sonic hedgehog (SHH) and fibroblast growth factors (FGFs) are key signalling molecules produced in the ZPA and AER, respectively. Experiments in chicks suggested that SHH expression in the ZPA is maintained by FGF4 expression in the AER, and vice versa, providing a molecular mechanism for coordinating the activities of these two signalling centres. This SHH/FGF4 feedback loop model is supported by genetic evidence showing that Fgf4 expression is not maintained in Shh-/- mouse limbs. We report here that Shh expression is maintained and limb formation is normal when Fgf4 is inactivated in mouse limbs, thus contradicting the model. We also found that maintenance of Fgf9 and Fgf17 expression is dependent on Shh, whereas Fgf8 expression is not. We discuss a model in which no individual Fgf expressed in the AER (AER-Fgf) is solely necessary to maintain Shh expression, but, instead, the combined activities of two or more AER-Fgfs function in a positive feedback loop with Shh to control limb development.
Similar articles
- Fgf8 signalling from the AER is essential for normal limb development.
Lewandoski M, Sun X, Martin GR. Lewandoski M, et al. Nat Genet. 2000 Dec;26(4):460-3. doi: 10.1038/82609. Nat Genet. 2000. PMID: 11101846 - Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds.
Zúñiga A, Haramis AP, McMahon AP, Zeller R. Zúñiga A, et al. Nature. 1999 Oct 7;401(6753):598-602. doi: 10.1038/44157. Nature. 1999. PMID: 10524628 - Shh, Bmp-2 and Hoxd-13 gene expression in chick limb bud cells in culture.
Kimura J, Ide H. Kimura J, et al. Dev Growth Differ. 1998 Aug;40(4):457-64. doi: 10.1046/j.1440-169x.1998.t01-2-00011.x. Dev Growth Differ. 1998. PMID: 9727360 - Apical ectodermal ridge regulates three principal axes of the developing limb.
Lin GH, Zhang L. Lin GH, et al. J Zhejiang Univ Sci B. 2020 Oct.;21(10):757-766. doi: 10.1631/jzus.B2000285. J Zhejiang Univ Sci B. 2020. PMID: 33043642 Free PMC article. Review. - Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.
Bénazet JD, Zeller R. Bénazet JD, et al. Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a001339. doi: 10.1101/cshperspect.a001339. Cold Spring Harb Perspect Biol. 2009. PMID: 20066096 Free PMC article. Review.
Cited by
- A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2.
Losa M, Barozzi I, Osterwalder M, Hermosilla-Aguayo V, Morabito A, Chacón BH, Zarrineh P, Girdziusaite A, Benazet JD, Zhu J, Mackem S, Capellini TD, Dickel D, Bobola N, Zuniga A, Visel A, Zeller R, Selleri L. Losa M, et al. Nat Commun. 2023 Jul 6;14(1):3993. doi: 10.1038/s41467-023-39443-z. Nat Commun. 2023. PMID: 37414772 Free PMC article. - The WNT7A/WNT7B/GPR124/RECK signaling module plays an essential role in mammalian limb development.
Wang Y, Venkatesh A, Xu J, Xu M, Williams J, Smallwood PM, James A, Nathans J. Wang Y, et al. Development. 2022 May 1;149(9):dev200340. doi: 10.1242/dev.200340. Epub 2022 May 12. Development. 2022. PMID: 35552394 Free PMC article. - Wnt Signaling Coordinates the Expression of Limb Patterning Genes During Axolotl Forelimb Development and Regeneration.
Lovely AM, Duerr TJ, Qiu Q, Galvan S, Voss SR, Monaghan JR. Lovely AM, et al. Front Cell Dev Biol. 2022 Apr 21;10:814250. doi: 10.3389/fcell.2022.814250. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 35531102 Free PMC article. - Sonic hedgehog is Essential for Proximal-Distal Outgrowth of the Limb Bud in Salamanders.
Purushothaman S, Lopez Aviña BB, Seifert AW. Purushothaman S, et al. Front Cell Dev Biol. 2022 Apr 1;10:797352. doi: 10.3389/fcell.2022.797352. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 35433673 Free PMC article. - A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies.
Tiu GC, Kerr CH, Forester CM, Krishnarao PS, Rosenblatt HD, Raj N, Lantz TC, Zhulyn O, Bowen ME, Shokat L, Attardi LD, Ruggero D, Barna M. Tiu GC, et al. Dev Cell. 2021 Jul 26;56(14):2089-2102.e11. doi: 10.1016/j.devcel.2021.06.013. Epub 2021 Jul 8. Dev Cell. 2021. PMID: 34242585 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials