Meeting Abstract

P1.62  Tuesday, Jan. 4  Deficiency of Tbx5a during zebrafish development results in altered cardiomyocyte morphology. PARRIE, Lindsay E*; CHERNYAVSKAYA, Yelena A; GARRITY, Deborah M; Colorado State University lparrie@mail.colostate.edu

Tbx5, a T-box transcription factor, is required for cardiac development. Mutations of Tbx5 lead to Holt-Oram Syndrome (HOS) in humans. As in HOS, mutation of zebrafish tbx5a affects both heart and forelimbs structures. Homozygous tbx5a/heartstrings (hst) exhibit bradycardia, failure of the heart tube to loop, cardiac edema and absence of pectoral fins. Here, we investigate the effects of tbx5a mutation on 1) cell proliferation in the developing heart tube, 2) volumetric growth of cardiomyocytes, and 3) myofibrillogenesis. Previous tbx5 overexpression studies in chick and mouse demonstrated that Tbx5 provides a growth arrest signal that limits cardiomyocyte proliferation during chamber morphogenesis stages (Liberatore et al., 2000). In the converse experiment we find that a tbx5a loss-of-function mutation in zebrafish did not lead to increased cardiomyocyte number, and had no net effect on cell proliferation of cardiomyocytes at 48 or 72 hours post-fertilization. We hypothesize that inability of the hst heart tube to loop may result from deficiencies in cardiomyocyte size and elongation of inner curvature cells. We provide an update on ongoing work to determine the earliest developmental timepoints at which tbx5a is necessary for normal cardiac function.