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Analysis of the bHLH transcription factor Delilah protein interactome in Drosophila with tandem affinity purification-mass spectrometry
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
Manuscript (Other academic)
URN: urn:nbn:se:umu:diva-3567OAI: diva2:142332
Available from: 2008-10-29 Created: 2008-10-29 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Identification of downstream targets of Alk signaling in Drosophila melanogaster
Open this publication in new window or tab >>Identification of downstream targets of Alk signaling in Drosophila melanogaster
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The Drosophila gene Anaplastic lymphoma kinase (Alk) is homologous to mammalian ALK, a member of the Alk/Ltk family of receptor tyrosine kinases. In Drosophila Alk is crucial for development of the embryonic visceral mesoderm, where it is the receptor for Jelly Belly (Jeb) ligand. Jeb binding stimulates an Alk-driven, extracellular signal-regulated, kinase-mediated signaling pathway, which results in the expression of the downstream gene duf/kirre. The visceral mesoderm is made up from two different cell types, founder cells and fusion competent myoblasts. The Jeb-Alk signal transduction pathway drives specification of the founder cells of the Drosophila visceral muscle. In this work we aimed to identify genes specifically expressed in the founder cells and/or fusion competent myoblasts. Four genes from a number of candidiates were investigated further. These genes are Hand, expressed in founder cells, goliath, parcas and delilah, which are expressed in fusion competent myoblasts. Hand is a basic helix-loop-helix (bHLH) transcription factor. Alk-mediated signal transduction drives the expression of the bHLH transcription factor hand in vivo, and loss of Alk function results in a complete lack of hand expression in the visceral mesoderm, while Alk gain of function results in an expansion of hand expression. There are no obvious defects in the visceral muscle fusion process hand mutant animals, suggesting that Hand is not critical for visceral muscle fusion per se.

I have studied another molecule Goliath, a putative RING finger E3 ligase. goliath is specifically expressed in the FCM of visceral and somatic muscles. goliath mutant animals do not display any obvious muscle phenotypes, perhaps reflecting a redundant role with CG10277, which encodes a second Goliath family protein in Drosophila. Deletion mutation of the CG10277 locus does not result in muscle defects either, and generation of double mutants of goliath and CG10277 will be required to determine their function in vivo.

In addition, I have studied another bHLH transcription factor Delilah and its role in muscle development. We show that delilah is expressed in visceral muscle, somatic muscles and in tendon cells. Delilah mutant animals display a held out wing phenotype and are unable to fly. Inducible RNAi against delilah results in a similar phenotype. Delilah is transcriptionally regulated by mef2 and biniou, early regulators of muscle development. While delilah appears to function in tendon cells, we were unable to find any obvious phenotype in either visceral or somatic muscles. In order to further investigate the underlying mechanism of Delilah function we have used Tandem affinity purification (TAP) methodology followed by mass spectrometry to identify Delilah binding partners. This analysis suggests a number of candidate functional partners for the Delilah protein.

Place, publisher, year, edition, pages
Umeå: Umeå centrum för molekylär patogenes (UCMP) (Medicinska fakulteten), 2008. 65 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1223
Drosophila, Alk, Jeb, visceral muscles, somatic muscles, Delilah, Goliath, Hand
National Category
Biochemistry and Molecular Biology
urn:nbn:se:umu:diva-1894 (URN)978-91-7264-668-1 (ISBN)
Public defence
2008-11-17, Betula, Bldg 6M, Umea University, Umea, 09:00 (English)
Available from: 2008-10-29 Created: 2008-10-29 Last updated: 2010-01-18Bibliographically approved

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