QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 10 December 2003
doi: 10.1242/dev.00940

This Article Figures Only Full Text Full Text (PDF) Supplemental Table All Versions of this Article: dev.00940v1 131/2/325    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hajihosseini, M. K. Articles by Heath, J. K. Search for Related Content PubMed PubMed Citation Articles by Hajihosseini, M. K. Articles by Heath, J. K.

Skeletal development is regulated by fibroblast growth factor receptor 1 signalling dynamics

Mohammad K. Hajihosseini^1,*,, Maria D. Lalioti^1,,, Sandrine Arthaud¹, Helen R. Burgar¹, Jill M. Brown², Stephen R. F. Twigg², Andrew O. M. Wilkie² and John K. Heath^1,

¹ School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
² Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK

Author for correspondence (e-mail: j.k.heath{at}bham.ac.uk)

Accepted 14 October 2003

Ligand-dependent signalling pathways have been characterised as having morphogen properties where there is a quantitative relationship between receptor activation and response, or threshold characteristics in which there is a binary switch in response at a fixed level of receptor activation. Here we report the use of a bacterial artificial chromosome (BAC)-based transgenic system in which a hypermorphic mutation has been introduced into the murine Fgfr1 gene. These mice exhibit cranial suture and sternal fusions that are exacerbated when the BAC copy number is increased. Surprisingly, increasing mutant BAC copy number also leads to the de novo appearance of digit I polydactyly in the hind limb and transformations of the vertebrae. Polydactyly is accompanied by a reduction of programmed cell death in the developing hind limb. Candidate gene analysis reveals downregulation of Dkk1 in the digit I field and upregulation of Wnt5a and Hoxd13. These findings show that Fgfr1-mediated developmental pathways exhibit differing signalling dynamics, whereby development of the cranial sutures and sternum follows a morphogen mode, whereas development of the vertebral column and the hind limbs has threshold signalling properties.

Key words: Fgf, Signalling, Skeleton

This article has been cited by other articles:

				A. Badde and D. Schulte A Role for Receptor Protein Tyrosine Phosphatase {lambda} in Midbrain Development J. Neurosci., June 11, 2008; 28(24): 6152 - 6164. [Abstract] [Full Text] [PDF]

				P. Lu, G. Minowada, and G. R. Martin Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function Development, January 1, 2006; 133(1): 33 - 42. [Abstract] [Full Text] [PDF]

				C. Li, X. Xu, D. K. Nelson, T. Williams, M. R. Kuehn, and C.-X. Deng FGFR1 function at the earliest stages of mouse limb development plays an indispensable role in subsequent autopod morphogenesis Development, November 1, 2005; 132(21): 4755 - 4764. [Abstract] [Full Text] [PDF]

				T. G. Smith, D. Sweetman, M. Patterson, S. M. Keyse, and A. Munsterberg Feedback interactions between MKP3 and ERK MAP kinase control scleraxis expression and the specification of rib progenitors in the developing chick somite Development, March 15, 2005; 132(6): 1305 - 1314. [Abstract] [Full Text] [PDF]

				S. Sudhop, F. Coulier, A. Bieller, A. Vogt, T. Hotz, and M. Hassel Signalling by the FGFR-like tyrosine kinase, Kringelchen, is essential for bud detachment in Hydra vulgaris Development, August 15, 2004; 131(16): 4001 - 4011. [Abstract] [Full Text] [PDF]