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Functional conservation of zinc-finger homeodomain gene zfh1/SIP1 in Drosophila heart development

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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.

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Abbreviations

CNS:

central nervous system

δEF1:

delta EF1

SBD:

smad binding protein

SIP1 :

Smad-interacting protein 1

zfh1 :

zinc-finger homeodomain protein 1

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Acknowledgements

We thank Zhi-Chen Lai, Manfred Frasch, Bruce Paterson, Talila Volk, and Michel Sémériva, Bloomington stock center, and Developmental Studies for Hybridoma Bank for providing fly stocks and valuable antibodies for this study. MKL was funded by a scientist development grant from the American Heart Association. This work was funded by grants from the National Institute of Health (NHLBI) to RB.

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Authors and Affiliations

  1. Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, 48109, USA

    Margaret Liu

  2. Department of Biology, National Taiwan Normal University, 88, sec. 4 Tingchou Road, Taipei, Taiwan, Republic of China

    Mingtsan Su

  3. Department of Anatomy, University of Wisconsin, Madison, WI, 53706, USA

    Gary E. Lyons

  4. Center for Neurosciences and Aging, Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Rolf Bodmer

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  1. Margaret Liu
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  2. Mingtsan Su
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  3. Gary E. Lyons
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  4. Rolf Bodmer
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Correspondence to Rolf Bodmer.

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Communicated by P. Simpson

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Liu, M., Su, M., Lyons, G.E. et al. Functional conservation of zinc-finger homeodomain gene zfh1/SIP1 in Drosophila heart development. Dev Genes Evol 216, 683–693 (2006). https://doi.org/10.1007/s00427-006-0096-1

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