EXOGENOUS RETINOIC ACID DURING GASTRULATION INDUCES CARTILAGINOUS ANDOTHER CRANIOFACIAL DEFECTS IN FUNDULUS-HETEROCLITUS

Embryonic levels of retinoic acid (RA) and the response of cells to RA are critical to the normal development of vertebrates. To understand the effects of RA signaling in Fundulus heteroclitus, we exposed embry os to a range of RA concentrations for 2 h during gastrulation. Embryo s exposed to low concentrations of RA (10(-10)-10(-7) M) develop norma lly, whereas those exposed to higher concentrations (5 X 10(-7)-10(-4) M) develop characteristic dose-dependent defects. We describe, in det ail, four stages of development that represent morphological effects o f RA on (1) cell death and defects in the brain, heart, and eye, (2) r elative size and differentiation, (3) duplications of pectoral fins, a nd (4) deletions in craniofacial cartilage elements. Analysis of carti laginous skeletal elements demonstrates distinct patterns of deletions in the neurocranium and pharyngeal skeleton in response to increasing concentrations of RA. In F. hereroclitus, RA treatment during gastrul ation results in five highly consistent phenotypes, which we have inco rporated into an index of embryonic RA defects. This index should be v aluable in the genetic analysis of RA pathways and in evaluating chemi cals that interfere with embryonic RA signaling.