Molecular and cellular basis of pattern formation during vertebrate limb development.
The body plan is generated by cells and tissues that become arranged precisely in the embryo. This process, termed pattern formation, involves cell interactions in which a particular group of cells produce signals that specify new cell types or patterns of differentiation in responding cells. These patterning signals emanate from very discrete centers called "organizer centers," such as the Hensen's node or Spemann organizer, the midbrain-hindbrain junction, the notochord, or in the case of the limb, the zone of polarizing activity (ZPA) or the apical ectodermal ridge (AER). The developing vertebrate limb is an ideal model system for the study of pattern formation because, in addition to surgical manipulations, molecular manipulations are now feasible. In this review we summarize early experiments that established, by means of surgical manipulations, the different organizer centers of the vertebrate limb: the ectoderm covering the limb bud, the apical ectodermal ridge, the zone of polarizing activity, and the distal mesoderm (progress zone) underlying the AER. We then describe the domains of expression of various genes present during the development of the limb and discuss some of the functional approaches (overexpression and lack of function studies) undertaken to ascertain their role in limb outgrowth. The knowledge acquired in the last few years has had an enormous impact not only on our view of how limbs develop (perhaps now one of the most approachable vertebrate model systems) but also in a more general sense of how the embryo is organized in space and time.
Gene Expression Laboratory, Salk Institute, La Jolla, California 92037, USA.
J K
JK
Ng
K
K
Tamura
D
D
Büscher
J C
JC
Izpisúa-Belmonte
D000818:Animals; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D002642:Chick Embryo; D004475:Ectoderm / Q000166:cytology / Q000637:transplantation; D005121:Extremities / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D008648:Mesoderm / Q000637:transplantation; D014714:Vertebrates / Q000196:embryology* / Q000235:genetics
D005346:Fibroblast Growth Factors