Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb

Butterfield, N. C., Metzis, V, McGlinn, E, Bruce, S. J., Wainwright, B. J. and Wicking, C (2009) Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb. DEVELOPMENT, 136 20: 3515-3524. doi:10.1242/dev.037507

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Author Butterfield, N. C.
Metzis, V
McGlinn, E
Bruce, S. J.
Wainwright, B. J.
Wicking, C
Title Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb
Journal name DEVELOPMENT   Check publisher's open access policy
ISSN 0950-1991
Publication date 2009-10
Year available 2009
Sub-type Article (original research)
DOI 10.1242/dev.037507
Open Access Status File (Publisher version)
Volume 136
Issue 20
Start page 3515
End page 3524
Total pages 10
Editor Jim Smith
Place of publication Cambridge, England, U.K.
Publisher The Company of Biologists
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
Abstract The vertebrate hedgehog receptor patched 1 (Ptc1) is crucial for negative regulation of the sonic hedgehog (Shh) pathway during anterior-posterior patterning of the limb. We have conditionally inactivated Ptc1 in the mesenchyme of the mouse limb using Prx1-Cre. This results in constitutive activation of hedgehog (Hh) signalling during the early stages of limb budding. Our data suggest that variations in the timing and efficiency of Cre-mediated excision result in differential forelimb and hindlimb phenotypes. Hindlimbs display polydactyly (gain of digits) and a molecular profile similar to the Gli3 mutant extra-toes. Strikingly, forelimbs are predominantly oligodactylous (displaying a loss of digits), with a symmetrical, mirror-image molecular profile that is consistent with re-specification of the anterior forelimb to a posterior identity. Our data suggest that this is related to very early inactivation of Ptc1 in the forelimb perturbing the gene regulatory networks responsible for both the pre-patterning and the subsequent patterning stages of limb development. These results establish the importance of the downstream consequences of Hh pathway repression, and identify Ptc1 as a key player in limb patterning even prior to the onset of Shh expression.
Keyword Patched 1
Sonic hedgehog signalling
Limb development
Shh/Grem1/FGF loop
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 03 Mar 2010, 15:15:13 EST by Susan Allen on behalf of Institute for Molecular Bioscience