Robert A. Holmgren / Professor / Biochemistry, Molecular Biology, and Cell Biology / PhD Harvard
r-holmgren@northwestern.edu
(847) 491-5460
(847) 491-4729
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Cell-fate specification during development.

Our laboratory studies the process of pattern formation during animal development. Recent work has focused on the Hedgehog (Hh) signal transduction pathway and its role in the patterning of Drosophila segments and appendages. The Hh pathway has been conserved throughout the animal kingdom and is also required for the development of vertebrate appendages, floorplate and many other structures. In flies the primary target of Hh signaling is the transcription factor Cubitus interruptus (Ci). In response to Hh signaling, cleavage of the Ci protein is blocked and Ci activates the expression of Hh target genes. We would like to understand in detail the regulation of Ci activity by signal transduction and the mechanism by which Ci acts with other factors to activate target genes. We have three major projects. The first uses a combination of genetic and structure-function studies to examine activities of various Ci protein domains. In the second, we are using genetic and molecular approaches to indentify new components of the Hh signal transduction pathway, and in the third, molecular and biochemical experiments are being used to study the regulation of enhancers by Ci. Through this work, we hope to understand how cells integrate different signaling systems and have their fates specified.

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Croker, J.A., Ziegenhorn, S.L. and Holmgren, R.A. (2006). Regulation of the Drosophila Transcription Factor, Cubitus interruptus, by Two Conserved Domains. Devel. Biol. 291:368-381.

Sisson, B.E., Ziegenhorn, S.L. and Holmgren R.A. (2006). Regulation of Ci and Su(fu) Nuclear Import in Drosophila. Devel. Biol. 294:258-270.

Tian, L., Holmgren, R.A. and Matouschek, A. (2005) A conserved processing mechanism regulates the activity of transcription factors Cubitus interruptus and NF-kB. Nature Struct. Mol. Biol. 12, 1045-53.

Lefers M.A., Wang, Q.T., Holmgren, R.A. (2001) Genetic dissection of the Drosophila Cabitus interruptus Signaling Complex. Dev. Bio. 236 (2):411-420.

Q.T. Wang and R.A. Holmgren (2000). Nuclear import of Cubitus interruptus is regulated by Hedgehog via a mechanism distinct from Ci stabilization and Ci activation. Development 127: 3131-3139.

Q.T. Wang, and R.A. Holmgren (1999). The Subcellular localization and activity of Drosophila Cubitus interruptus is regulated at multiple levels. Development 126: 3669-3677.

J. Hepker, R. Blackman, and R.A. Holmgren (1999). Cubitus interruptus is necessary but not sufficient for direct activation of a wing specific decapentaplegic enhancer. Development 126: 3669-3677.

J. Hepker, Q. Wang, C. Motzny, R. Holmgren, and T. Orenic (1997). The Drosophila segment polarity gene cubitus interruptus mediates hedgehog signal transduction. Development 124: 549-558.

J. Skeath, Y. Zhang, R. Holmgren, S. Carroll, and C. Doe (1995). Specification of neuroblast identity in the Drosophila embryonic central nervous system by gooseberry-distal. Nature 376: 427-430.

D. E. Buenzow and R. Holmgren (1995). Expression of the Drosophila gooseberry locus defines a subset of lineages in the central nervous system. Devel. Biol. 170: 338-349.

C. Motzny and R. Holmgren (1995). The Drosophila cubitus interruptus protein and its roles in the wingless and hedgehog signal transduction pathways. Mech. of Devel. 52: 137-150.

View all publications by publications by Robert A. Holmgren listed in the National Library of Medicine (PubMed).

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