Affiliation:
1. Department of Zoology and Animal Biology and National Program Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Abstract
Anterior-to-posterior patterning, the process whereby our digits are differently shaped, is a key aspect of limb development. It depends on the localized expression in posterior limb bud of
Sonic hedgehog
(
Shh
) and the morphogenetic potential of its diffusing product. By using an inversion of and a large deficiency in the mouse
HoxD
cluster, we found that a perturbation in the early collinear expression of
Hoxd11, Hoxd12
, and
Hoxd13
in limb buds led to a loss of asymmetry. Ectopic
Hox
gene expression triggered abnormal
Shh
transcription, which in turn induced symmetrical expression of
Hox
genes in digits, thereby generating double posterior limbs. We conclude that early posterior restriction of
Hox
gene products sets up an anterior-posterior prepattern, which determines the localized activation of
Shh
. This signal is subsequently translated into digit morphological asymmetry by promoting the late expression of
Hoxd
genes, two collinear processes relying on opposite genomic topographies, upstream and downstream
Shh
signaling.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
253 articles.
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