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Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb.
- Source :
-
Development (Cambridge, England) [Development] 2009 Oct; Vol. 136 (20), pp. 3515-24. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Apoptosis
Embryo, Mammalian cytology
Embryo, Mammalian metabolism
Female
Hedgehog Proteins genetics
Kruppel-Like Transcription Factors genetics
Male
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins genetics
Patched Receptors
Patched-1 Receptor
Receptors, Cell Surface genetics
Signal Transduction
Up-Regulation
Zinc Finger Protein Gli3
Body Patterning
Extremities embryology
Gene Expression Regulation, Developmental
Receptors, Cell Surface metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 136
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 19783740
- Full Text :
- https://doi.org/10.1242/dev.037507