Abstract
LIMB development depends on signals from the apical ectodermal ridge and underlying mesenchyme1,2. Fibroblast growth factor (FGF) can replace the ridge3,4 and, because Fgf4RNA is localized to the mouse posterior ridge5, we proposed that FGF4 is the endogenous ridge signal3. Ridge signals control limb outgrowth and maintain the zone of polarizing activity (ZPA) at the limb posterior margin6, which is important in limb patterning: a ZPA graft to limb anterior mesenchyme causes cell respecification and mirror-image duplications1,2. Sonic hedgehog (SHH7,8) has polar-izing activity, and Shh RNA. co-localizes with ZPA activity, suggesting SHH is the endogenous polarizing signal7. We have investigated the molecular regulation of Fgf4 and Shh expression. We report here that Fgf4 expression in the ridge can be regulated byshh-expressing cells. Moreover, Shh expression in mesenchyme can be activated by FGF4 in combination with retinoic acid. Once induced, Shhexpression can be maintained by FGF4 alone, thus establishing a positive feedback loop between ZPA and ridge.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tickle, C. & Eichele, G. A. Rev. Cell Biol. 10, 121–152 (1994).
Tabin, C. J. Cell 66, 199–217 (1991).
Niswander, L., Tickle, C., Vogel, A., Booth, I. & Martin, G. R. Cell 75, 579–587 (1993).
Fallon, J. F. et al. Science 264, 104–107 (1994).
Niswander, L. & Martin, G. R. Development 114, 755–768 (1992).
Vogel, A. & Tickle, C. Development 119, 199–206 (1993).
Riddle, R. D., Johnson, R. L., Laufer, E. & Tabin, C. Cell 75, 1401–1416 (1993).
Roelink, H. et al. Cell 76, 761–775 (1994).
Lee, J. & Tickle, C. J. Embryol. exp. Morph. 90, 139–169 (1985).
Basilico, C. & Moscatelli, D. Adv. Cancer Res. 59, 115–165 (1992).
Han, J.-K. & Martin, G. R. Devl Biol. 158, 549–554 (1993).
de Lapeyrière, O. et al. Development 118, 601–611 (1993).
Koyama, E. et al. Dev. Growth Differ. 35, 189–198 (1993).
Izpisúa-Belmonte, J.-C., Brown, J. M., Duboule, D. & Tickle, C. EMBO J. 11, 1451–1457 (1992).
Izpisúa-Belmonte, J.-C., Tickle, C., Dollé, P., Wolpert, L. & Duboule, D. Nature 350, 585–589 (1991).
Eichele, G., Tickle, C. & Alberts, B. M. J. Cell Biol. 101, 1913–1920 (1985).
Anderson, R., Landry, M. & Muneoka, K. Development 117, 1421–1433 (1993).
Dono, R. & Zeller, R. Devl Biol. 163, 316–330 (1994).
Thaller, C. & Eichele, G. Nature 327, 625–628 (1987).
Hamburger, V. & Hamilton, H. L. Devl Dynam. 195, 231–272 (1992).
Hébert, J. M., Basilico, C., Goldfarb, M., Haub, O. & Martin, G. R. Devl Biol. 138, 454–463 (1990).
Izpisúa-Belmonte, J.-C., De Robertis, E. M., Storey, K. G. & Stern, C. D. Cell 74, 645–659 (1993).
Tickle, C., Lee, J. & Eichele, G. Devl Biol. 109, 82–95 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Niswander, L., Jeffrey, S., Martin, G. et al. A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature 371, 609–612 (1994). https://doi.org/10.1038/371609a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/371609a0
This article is cited by
-
Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning
Nature Communications (2023)
-
The hedgehog pathway and ocular developmental anomalies
Human Genetics (2019)
-
Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3
Scientific Reports (2018)
-
Santos syndrome is caused by mutation in the WNT7A gene
Journal of Human Genetics (2017)
-
Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes
Nature Communications (2017)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.