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Publication : Distinct functions of homeodomain-containing and homeodomain-less isoforms encoded by homothorax.

First Author  Noro B Year  2006
Journal  Genes Dev Volume  20
Issue  12 Pages  1636-50
PubMed ID  16778079 Mgi Jnum  J:109723
Mgi Id  MGI:3629545 Doi  10.1101/gad.1412606
Citation  Noro B, et al. (2006) Distinct functions of homeodomain-containing and homeodomain-less isoforms encoded by homothorax. Genes Dev 20(12):1636-50
abstractText  The homothorax (hth) gene of Drosophila melanogaster is required for executing Hox functions, for head development, and for forming the proximodistal (PD) axis of the appendages. We show that alternative splicing of hth generates two types of protein isoforms, one that contains a DNA-binding homeodomain (HthFL) and one that does not contain a homeodomain (HDless). Both types of Hth isoforms include the evolutionarily conserved HM domain, which mediates a direct interaction with Extradenticle (Exd), another homeodomain protein. We show that although both HthFL and HDless isoforms of Hth can induce the nuclear localization of Exd, they carry out distinct sets of functions during development. Surprisingly, we find that many of hth's functions, including PD patterning and most Hox-related activities, can be executed by the HDless isoforms. In contrast, antennal development shows an absolute dependency on the HthFL isoform. Thus, alternative splicing of hth results in the generation of multiple transcription factors that execute unique functions in vivo. We further demonstrate that the mouse ortholog of hth, Meis1, also encodes a HDless isoform, suggesting that homeodomain-less variants of this gene family are evolutionarily ancient.
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