Anteroposterior patterning in the limb and digit specification: contribution of mouse genetics.
The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results.
Robert
Benoît
B
Department of Developmental Biology, CNRS URA 2578, Pasteur Institute, Paris, France. brobert@pasteur.fr
Lallemand
Yvan
Y
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D005121:Extremities / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005801:Genes, Homeobox; D053823:Hedgehog Proteins; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D005810:Multigene Family; D009154:Mutation; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D012097:Repressor Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D014212:Tretinoin