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Zhe Han, Peng Yi, Eric Olson. Dept Molecular
Biol, Univ Texas SW Medical Ctr, Dallas, TX.
The Hand family of basic Helix-Loop-Helix
(bHLH) transcription factors plays critical roles in cardiovascular
development in vertebrates, but little is known about the single
Hand gene in Drosophila. Here, we show that Drosophila Hand is
expressed in cardioblasts, pericardial nephrocytes and hematopoietic
progenitors. The homeodomain protein Tinman and the GATA factors,
Pannier and Serpent, directly activate Hand in these cell types
through a minimal enhancer, which is necessary and sufficient to
drive Hand expression in these cell types composing the circulatory
system. Using cell culture and in vivo over-expression
assays, we show that Drosophila Hand is a potent transcriptional
activator required for development of the heart and lymph gland.
Disruption of Hand function by homologous recombination results in
embryonic and larval lethality accompanied by profound heart defects
that include hypoplastic myocardium and a deficiency of pericardial
and lymph gland hematopoietic precursor cells, accompanied by
ectopic apoptosis in these organs. These abnormalities can be
rescued by targeted expression of a human Hand gene, as well as the
caspase inhibitor p35. These findings place hand at a nexus of the
transcriptional networks that govern cardiogenesis and hematopoiesis,
and reveal evolutionarily conserved functions of Hand transcription
factors in the control of cell survival during cardiogenesis and
hematopoiesis. |
