Originally published as Genetics Published Articles Ahead of Print on February 3, 2008.

Genetics, Vol. 178, 1399-1413, March 2008, Copyright © 2008
doi:10.1534/genetics.107.081638

A Screen for Modifiers of Hedgehog Signaling in Drosophila melanogaster Identifies swm and mts

David J. Casso*, Songmei Liu*, D. David Iwaki*, Stacey K. Ogden{dagger} and Thomas B. Kornberg*,1

* Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2711 and {dagger} Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755

1 Corresponding author: Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2711.
E-mail: tkornberg{at}biochem.ucsf.edu

Signaling by Hedgehog (Hh) proteins shapes most tissues and organs in both vertebrates and invertebrates, and its misregulation has been implicated in many human diseases. Although components of the signaling pathway have been identified, key aspects of the signaling mechanism and downstream targets remain to be elucidated. We performed an enhancer/suppressor screen in Drosophila to identify novel components of the pathway and identified 26 autosomal regions that modify a phenotypic readout of Hh signaling. Three of the regions include genes that contribute constituents to the pathway—patched, engrailed, and hh. One of the other regions includes the gene microtubule star (mts) that encodes a subunit of protein phosphatase 2A. We show that mts is necessary for full activation of Hh signaling. A second region includes the gene second mitotic wave missing (swm). swm is recessive lethal and is predicted to encode an evolutionarily conserved protein with RNA binding and Zn+ finger domains. Characterization of newly isolated alleles indicates that swm is a negative regulator of Hh signaling and is essential for cell polarity.


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Genetics 2008 178: NP. [Full Text]