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Journal of Anatomy logoLink to Journal of Anatomy
. 2002 Nov;201(5):417. [Article in Spanish] doi: 10.1046/j.1469-7580.2002.01021.x

1 Patterning the limb before and after SHH

P te Welscher 1, A Zuniga 1, M Fernandez-Teran 2, M Ros 2, S Kuijper 3, T Drenth 1, H Goedemans 1, F Meijlink 3, Rolf Zeller 1
PMCID: PMC1570940  PMID: 17103744

Abstract

The Summer Meeting of the Anatomical Society of Great Britain and Ireland was held at the University of Dundee, from 23rd to 25th July 2002. It included a symposium on ‘How to make a hand’. The following are abstracts of communications and posters presented at the meeting.


SHH signalling by the polarising region in the posterior limb bud mesenchyme controls distal limb patterning and specification of digit identities in tetrapods. Furthermore it has been generally accepted that ectopic anterior SHH signalling is a major cause of preaxial polydactyly in mice and humans. However analysis of Shh/Gli3 compound mutant embryos reveals that the preaxial polydactyly of Gli3 deficient mice arises completely independent of SHH signalling, while no digit arch forms in Shh single mutant limb buds. The Shh independent restoration of distal limb development is Gli3 gene dose dependent, as disruption of one or both Gli3 alleles in Shh deficient mouse embryos results in progressive restoration of distal limb development and digit formation. Molecular and genetic analysis establishes that GLI3 functions initially upstream of SHH to restrict dHAND expression to the posterior limb bud mesenchyme. In turn, dHAND keeps Gli3 anteriorly restricted and participates in activation of SHH signalling. Subsequently SHH signalling by the polarising region is crucial to counteract GLI3 repression to enable maintenance of key regulator genes such as 5′Hox genes and thereby distal progression of limb bud patterning. The implications of these genetic results with respect to our current understanding of limb evolution will be discussed.


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