Congress Abstracts - Society for Developmental Biology

Urness, Lisa D; Bleyl, Steven B (University of Utah, USA); Moon, Anne M (Weis Center for Research/Geisinger Clinic, USA);
Mansour, Suzanne L. (Univ of Utah, USA)
The heart forms from multipotent progenitors and abnormalities within the progenitors or in their interactions with surrounding cells
lead to congenital heart defects. One progenitor, the proepicardial organ (PEO), forms in mesothelium caudal to the developing heart.
PEO cells migrate across pericardial space, attach to the myocardium and migrate over the myocardial surface to form the epicardium
by E11.5 in mouse. Some epicardial cells undergo an epithelial-to-mesenchymal transition and enter the heart, generating coronary
smooth muscle, endothelium and fibroblasts. The epicardium also provides trophic signals supporting expansion of the myocardium
during mid-gestation. Fibroblast growth factors (FGFs) provide critical communication within and between developing heart
progenitors and surrounding tissues. Global Fgf3/Fgf10 double null mutants exhibit a spectrum of heart defects not found in either
single null mutant. Defects include reduced epicardial cell ensheathment, detachment of epicardial cells from the myocardium, and
thinned myocardium, with double mutants dying of heart failure by E11.0. Fgf10 is expressed in cardiac mesoderm and the PEO, but
the Fgf3 expression domain relevant to the epicardial phenotype is unclear. To determine the earliest role of PEO-derived cells in
murine cardiac development, we are genetically ablating Tbx18+ PEO cells and have found that their loss causes heart failure and
death by E11.5. To determine the tissue-specific requirements for Fgf10 and Fgf3 in heart development we are conducting conditional
mutant analyses. Our data suggest that Fgf10 is required in the proepicardium and cardiac mesoderm and that there may be a
mesodermal source of Fgf3 important for heart development.
Program/Abstract # 365
Arid3b is required for the formation of heart poles and patterning of the atrioventricular canal (AVC)
Uribe Sokolov, Veronica; Badia-Careaga, Claudio (CNIC, Spain); Casanova, Jesus (Monash University, Australia); Sanz-Ezquerro,
Juan Jose (CNB, Spain)
ARID3b is a member of the conserved ARID family of gene regulators, which is known to have important roles in both embryonic
development and cancer. ARID3b null-mice die during early stages of embryonic development, but its roles in development are not
completely understood. The purpose of our study is to address the function of Arid3b in the developing heart. During mouse embryo
development Arid3b is expressed from early stages in the myocardium of the tubular heart and in the precursors situated in the
pharyngeal mesoderm (second heart field), but later it gets restricted to the poles of the heart. Using Arid3b knock-out mice, we
observed that mutants display cardiac abnormalities. Three main defects are seen – a noticeable shortening of the outflow tract, a
reduction of the size and abnormal shape of the inflow region and a premature maturation of the myocardium of the AVC, as well as a
fail to form the AV cushions. Expression of several molecular markers of both secondary heart field (SHF) and chambers are altered
in mutant embryos. To address the cause of the defects in the heart poles, we performed DiI labelling of heart precursors and in vitro
embryo culture, observing a reduction in the addition of cells to the heart tube. An RNA microarray comparing wild type versus
mutant hearts revealed a set of differentially expressed genes, which are now being analyzed. Our conclusion is that Arid3b plays an
important role in different aspects of heart development. In vivo embryonic phenotypes, DiI labelling experiments and in vitro cell
culture data suggest that Arid3b could control cell addition from the SHF to the heart by regulating cell motility. Moreover, Arid3b is
involved in proper chamber and valve formation.
Program/Abstract # 366
Elucidating Mechanisms Underlying Epicardial Development
Khan, Sana; Holtzman, Nathalia (Queens College, USA)
Heart organogenesis requires the coordination of cells and development of three cardiac tissue layers. The muscular myocardium is
internally lined by the endocardium and externally covered by the epicardium. The stem-cell-like quality of epicardial cells is essential
for development and regeneration of some cardiac tissues. The epicardium signals to and contributes cells to coronary vessels,
myocardium, and endocardium. Despite its importance, the process required to form and mature the epicardium is poorly understood.
Previous studies suggest that cells from the proepicardial organ (PEO) at the base of the sinus venosus (SV) migrate onto the
myocardium via direct contact of PEO derived multicellular structures and indirectly through cellular cysts that float across to the
myocardium to form epicardium. Taking advantage of the optical clarity, cardiac morphology and molecular tools available in
zebrafish, we find evidence for two mechanisms of PEO migration. The primary PEO population sits at the SV. A subset of cells from
SV PEO crawl directly onto the atrial myocardium, the direct migrators. A second set of cells, indirect migrators, travel along the
pericardial surface posterior to the myocardium. In the region posterior to the AV myocardium, we observe clusters of cells, the AV
PEO. We found that AV PEO cells form mulitcellular villi that transfer cells via cardiac contractions and differential adhesion to the
ventricular myocardium. We tested this mechanism by disrupting cardiac contractility with drug treatment. Significantly fewer PEO
villi cells transferred to the ventricle surface when cardiac contractions were abolished. PEO villi cell migration to the ventricular
myocardium is cardiac contraction dependent.
Program/Abstract # 367
The role of Fosl2 in zebrafish Second Heart Field Development
Jahangiri, Leila; Guner-Ataman, Burcu; Adams, Meghan; Burns, Caroline E; Burns, C. Geoffrey (MGH, Harvard Medical School,
USA)
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