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Appendix - CNIC

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SCIENTIFIC REPORT ´09 1 Cardiovascular Developmental Biology<br />

Role of new genes<br />

in cardiovacular development<br />

> RESEARCH INTEREST<br />

Head of Laboratory: Juan José Sanz Ezquerro<br />

Predoctoral Researchers: Jesús Chamorro Casanova<br />

Verónica Uribe Sokolov<br />

Masters student: Laura González Calero<br />

Our laboratory combines studies in chick and mouse embryos<br />

with in vitro cell culture strategies to address the role of new<br />

genes in the development of the cardiovascular system and<br />

in particular the morphogenesis of the heart. Our recent work<br />

has examined the role of AT-rich interactive domaincontaining<br />

protein 3B (Arid3b) during heart formation.<br />

Arid3b is a transcription factor of the highly conserved ARID<br />

family, whose members share a common DNA-binding<br />

domain. Arid3b null-mice die early in embryonic<br />

development and their phenotype includes severe defects in<br />

many structures, especially the heart. However, the exact<br />

roles of Arid3b in development remain unclear.<br />

Examination of the pattern of Arid3b expression shows that it<br />

is expressed at early stages of development in the heart tube<br />

Technician: Claudio Badía Careaga<br />

and is later restricted to the myocardium of the outflow tract,<br />

right ventricle, atria and sinus venosus. We are currently<br />

carrying out anatomical, histological, cellular and molecular<br />

analyses to characterize the cardiac defects produced by the<br />

absence of the Arid3b gene. Our results so far identify a<br />

major defect in outflow tract formation in Arid3b knockout<br />

mice.<br />

Our data also indicate that Arid3b regulates the contribution<br />

to the heart of cells from the secondary heart field. We plan<br />

to analyze the cellular basis of these Arid3b functions—for<br />

example its possible involvement in cell migration—and to<br />

identify its molecular targets by microarray analyses.<br />

Proliferation (green labeling by anti-PH3) and apoptosis (red labeling by TUNEL) in Arid3b knockout embryos at E9. At this<br />

stage, embryos show no apparent heart defects, but there is a clear increase in the number of dead cells in cranial<br />

mesenchyme.<br />

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