The Drosophila Hand gene is required for remodeling of the developing adult heart and midgut during metamorphosis.
The Hand proteins of the bHLH family of transcriptional factors play critical roles in vertebrate cardiogenesis. In Drosophila, the single orthologous Hand gene is expressed in the developing embryonic dorsal vessel (heart), lymph glands, circular visceral musculature, and a subset of CNS cells. We demonstrate that the absence of Hand activity causes semilethality during the early larval instars. The dorsal vessel and midgut musculature are unaffected in null mutant embryos, but in a large fraction the lymph glands are missing. However, homozygous adult flies lacking Hand possess morphologically abnormal dorsal vessels characterized by a disorganized myofibrillar structure, reduced systolic and diastolic diameter, and abnormal heartbeat contractions, and suffer from premature lethality. In addition, their midguts are highly deformed; in the most severe cases, there is midgut blockage and a massive excess of ectopic peritrophic membrane tubules exiting a rupture in an anterior midgut bulge. Nevertheless, the visceral musculature appears to be relatively normal. Based on these phenotypes, we conclude that the expression of the Drosophila Hand gene in the dorsal vessel and circular visceral muscles is mainly required during pupal stages, when Hand participates in the proper hormone-dependent remodeling of the larval aorta into the adult heart and in the normal morphogenesis of the adult midgut endoderm during metamorphosis.
Lo
Patrick C H
PC
Brookdale Department of Molecular, Cell and Developmental Biology, Box 1020, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Zaffran
Stéphane
S
Sénatore
Sébastien
S
Frasch
Manfred
M
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D005260:Female; D041981:Gastrointestinal Tract / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D006339:Heart Rate; D008675:Metamorphosis, Biological; D009024:Morphogenesis; D009154:Mutation; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; C475488:Hand protein, Drosophila