title: Functional conservation of zinc-finger homeodomain gene zfh1/SIP1 in Drosophila heart development.
abstract: Comparative genetic studies of diverse animal model systems have revealed that similar developmental mechanisms operate across the Metazoa. In many cases, the genes from one organism can functionally replace homologues in other phyla, a result consistent with a high degree of evolutionarily conserved gene function. We investigated functional conservation among the Drosophila zinc-finger homeodomain protein 1 (zfh1) and its mouse functional homologue Smad-interacting protein 1 (SIP1). Northern blot analyses of SIP1 expression patterns detected three novel variants (8.3, 2.7, and 1.9 kb) in addition to the previously described 5.3 kb SIP1 transcript. The two shorter novel SIP1 transcripts were encountered only in developing embryos and both lacked zinc-finger clusters or homeodomain regions. The SIP1 transcripts showed complex embryonic expression patterns consistent with that observed for Drosophila zfh1. They were highly expressed in the developing nervous systems and in a number of mesoderm-derived tissues including lungs, heart, developing myotomes, skeletal muscle, and visceral smooth muscle. The expression of the mammalian 5.3 kb SIP1 transcript in Drosophila zfh1 null mutant embryos completely restored normal heart development in the fly, demonstrating their functional equivalence in cardiogenic pathways. Our present data, together with the previously described heart defects associated with both SIP1 and Drosophila zfh1 mutations, solidify the conclusion that the zfh1 family members participate in an evolutionary conserved program of metazoan cardiogenesis.
authors.affiliation: Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, 48109, USA. rolf@burnham.org
authors.forename: Margaret
authors.initials: M
authors.lastname: Liu
authors.forename: Mingtsan
authors.initials: M
authors.lastname: Su
authors.forename: Gary E
authors.initials: GE
authors.lastname: Lyons
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D006321:Heart / Q000196:embryology*; D012097:Repressor Proteins / Q000235:genetics*; D016335:Zinc Fingers
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012097:Repressor Proteins; C081010:zfh1 protein, Drosophila