FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximodistal axis
- PMID: 18094024
- DOI: 10.1242/dev.013268
FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximodistal axis
Abstract
Fibroblast growth factors (FGFs) are signals from the apical ectodermal ridge (AER) that are essential for limb pattern formation along the proximodistal (PD) axis. However, how patterning along the PD axis is regulated by AER-FGF signals remains controversial. To further explore the molecular mechanism of FGF functions during limb development, we conditionally inactivated fgf receptor 2 (Fgfr2) in the mouse AER to terminate all AER functions; for comparison, we inactivated both Fgfr1 and Fgfr2 in limb mesenchyme to block mesenchymal AER-FGF signaling. We also re-examined published data in which Fgf4 and Fgf8 were inactivated in the AER. We conclude that limb skeletal phenotypes resulting from loss of AER-FGF signals cannot simply be a consequence of excessive mesenchymal cell death, as suggested by previous studies, but also must be a consequence of reduced mesenchymal proliferation and a failure of mesenchymal differentiation, which occur following loss of both Fgf4 and Fgf8. We further conclude that chondrogenic primordia formation, marked by initial Sox9 expression in limb mesenchyme, is an essential component of the PD patterning process and that a key role for AER-FGF signaling is to facilitate SOX9 function and to ensure progressive establishment of chondrogenic primordia along the PD axis.
Similar articles
-
FGF signals guide migration of mesenchymal cells, control skeletal morphogenesis [corrected] and regulate gastrulation during sea urchin development.Development. 2008 Jan;135(2):353-65. doi: 10.1242/dev.014282. Epub 2007 Dec 12. Development. 2008. PMID: 18077587
-
Effects of FGFs on the morphogenic potency and AER-maintenance activity of cultured progress zone cells of chick limb bud.Int J Dev Biol. 1998 May;42(4):591-9. Int J Dev Biol. 1998. PMID: 9694630
-
Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function.Development. 2006 Jan;133(1):33-42. doi: 10.1242/dev.02172. Epub 2005 Nov 24. Development. 2006. PMID: 16308330
-
[Signaling molecules involved in induction and early patterning of limb buds].Kaibogaku Zasshi. 1998 Dec;73(6):655-66. Kaibogaku Zasshi. 1998. PMID: 9990203 Review. Japanese.
-
Apical ectodermal ridge regulates three principal axes of the developing limb.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.
Cited by
-
Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning.Nat Commun. 2023 Sep 20;14(1):5841. doi: 10.1038/s41467-023-41457-6. Nat Commun. 2023. PMID: 37730682 Free PMC article.
-
The discovery, function, and regulation of epithelial splicing regulatory proteins (ESRP) 1 and 2.Biochem Soc Trans. 2023 Jun 28;51(3):1097-1109. doi: 10.1042/BST20221124. Biochem Soc Trans. 2023. PMID: 37314029 Free PMC article.
-
RAF1 deficiency causes a lethal syndrome that underscores RTK signaling during embryogenesis.EMBO Mol Med. 2023 May 8;15(5):e17078. doi: 10.15252/emmm.202217078. Epub 2023 Apr 17. EMBO Mol Med. 2023. PMID: 37066513 Free PMC article.
-
Sonic hedgehog is Essential for Proximal-Distal Outgrowth of the Limb Bud in Salamanders.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.
-
Biological Significance and Targeting of the FGFR Axis in Cancer.Cancers (Basel). 2021 Nov 13;13(22):5681. doi: 10.3390/cancers13225681. Cancers (Basel). 2021. PMID: 34830836 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous