The International Journal of Developmental Biology

Int. J. Dev. Biol. 49: 443 - 448 (2005)

Vol 49, Issue 4

Genetic interaction of Gli3 and Alx4 during limb development

Short Communication | Published: 1 June 2005

Lia Panman*, Thijs Drenth, Pascal teWelscher, Aimée Zuniga1 and Rolf Zeller1

Department of Developmental Biology, Utrecht University, Utrecht, The Netherlands and 1Developmental Genetics, DKBW Centre for Biomedicine, University of Basel Medical School, Basel, Switzerland.


The Gli3 and Alx4 transcriptional regulators are expressed in the anterior limb bud mesenchyme and their disruption in mice results in preaxial polydactyly. While the polydactylous phenotype of Alx4 deficient limb buds depends on SHH, the one of Gli3 deficient limb buds is completely independent of SHH signalling, suggesting that these genes act in parallel pathways. Analysis of limb buds lacking both Gli3 and Alx4 now shows that these two genes interact during limb skeletal morphogenesis. In addition to the defects in single mutants, the stylopod is severely malformed and the anterior element of the zeugopod is lost in double mutant limbs. However, limb bud patterning in Gli3-/- ; Alx4-/- double mutant embryos is not affected more than in single mutants as the expression domains of key regulators remain the same. Most interestingly, the loss of the severe preaxial polydactyly characteristic of Gli3 -/- limbs in double mutant embryos establishes that this type of polydactyly requires Alx4 function.


Hox gene, limb development, preaxial polydactyly, radius, SHH, tibia

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