Molecular approaches to vertebrate limb morphogenesis.
It has long been proposed that concentration gradients of morphogens provide cues to specify cell fate in embryonic fields. Recent work in a variety of vertebrate systems give bona fide evidence that retinoic acid, the biologically active form of vitamin A, is a candidate for such a morphogen. In the developing chick wing, for example, locally applied retinoic acid triggers striking changes in the pattern along the anteroposterior axis. Instead of giving rise to a wing with the normal 234 digit pattern, wing buds treated with retinoic acid develop a 432234 mirror-image symmetrical digit pattern. For this review, we focus on three aspects of limb morphogenesis. (1) We summarize the experimental evidence supporting the notion that retinoic acid is a candidate morphogen. (2) Limb buds contain high levels of cellular retinoic-acid-binding protein (CRABP). Using order of magnitude calculations, we evaluate how the concentration of CRABP might affect the occupancy state of the retinoic acid receptor. (3) We discuss the spatio-temporal expression pattern of homeobox-containing genes in the developing limb and speculate about the possibility that retinoic acid influences the pattern of expression of homeobox genes.
Smith
S M
SM
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115.
Pang
K
K
Sundin
O
O
Wedden
S E
SE
Thaller
C
C
Eichele
G
G
D000818:Animals; D005121:Extremities / Q000196:embryology*; D005801:Genes, Homeobox; D009024:Morphogenesis; D014212:Tretinoin / Q000494:pharmacology*; D014714:Vertebrates / Q000196:embryology*
D014212:Tretinoin