Alternative Splicing Modulates Ubx Protein Function in Drosophila Melanogaster
Copyright Ó 2010 by the Genetics Society of America DOI: 10.1534/genetics.109.112086 Alternative Splicing Modulates Ubx Protein Function in Drosophila melanogaster Hilary C. Reed,* Tim Hoare,† Stefan Thomsen,‡ Thomas A. Weaver,† Robert A. H. White,† Michael Akam* and Claudio R. Alonso‡,1 *Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom, †Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, United Kingdom and ‡School of Life Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom Manuscript received November 13, 2009 Accepted for publication December 17, 2009 ABSTRACT The Drosophila Hox gene Ultrabithorax (Ubx) produces a family of protein isoforms through alternative splicing. Isoforms differ from one another by the presence of optional segments—encoded by individual exons—that modify the distance between the homeodomain and a cofactor-interaction module termed the ‘‘YPWM’’ motif. To investigate the functional implications of Ubx alternative splicing, here we analyze the in vivo effects of the individual Ubx isoforms on the activation of a natural Ubx molecular target, the decapentaplegic (dpp) gene, within the embryonic mesoderm. These experiments show that the Ubx isoforms differ in their abilities to activate dpp in mesodermal tissues during embryogenesis. Furthermore, using a Ubx mutant that reduces the full Ubx protein repertoire to just one single isoform, we obtain specific anomalies affecting the patterning of anterior abdominal muscles, demonstrating that Ubx isoforms are not functionally interchangeable during embryonic mesoderm development. Finally, a series of experiments in vitro reveals that Ubx isoforms also vary in their capacity to bind DNA in presence of the cofactor Extradenticle (Exd).
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