Reiterative roles for FGF signaling in the establishment of size and proportion of the zebrafish heart.

Development of a functional organ requires the establishment of its proper size as well as the establishment of the relative proportions of its individual components. In the zebrafish heart, organ size and proportion depend heavily on the number of cells in each of its two major chambers, the ventricle and the atrium. Heart size and chamber proportionality are both affected in zebrafish fgf8 mutants. To determine when and how FGF signaling influences these characteristics, we examined the effect of temporally controlled pathway inhibition. During cardiac specification, reduction of FGF signaling inhibits formation of both ventricular and atrial cardiomyocytes, with a stronger impact on ventricular cells. After cardiomyocyte differentiation begins, reduction of FGF signaling can still result in a deficiency of ventricular cardiomyocytes. Consistent with two temporally distinct roles for FGF, we find that increased FGF signaling induces a cardiomyocyte surplus only before cardiac differentiation begins. Thus, FGF signaling first regulates heart size and chamber proportionality during cardiac specification and later refines ventricular proportion by regulating cell number after the onset of differentiation. Together, our data demonstrate that a single signaling pathway can act reiteratively to coordinate organ size and proportion.