A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response

Sekyung Oh; Masaki Kato; Chi Zhang; Yurong Guo; Philip A Beachy

doi:10.1371/journal.pone.0135804

A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response

PLoS One. 2015 Aug 13;10(8):e0135804. doi: 10.1371/journal.pone.0135804. eCollection 2015.

Authors

Sekyung Oh¹, Masaki Kato¹, Chi Zhang², Yurong Guo³, Philip A Beachy⁴

Affiliations

¹ Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America; Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
² Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
³ Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
⁴ Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America; Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Biochemistry, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America.

Abstract

Suppressor of fused (Su(fu)/Sufu), one of the most conserved components of the Hedgehog (Hh) signaling pathway, binds Ci/Gli transcription factors and impedes activation of target gene expression. In Drosophila, the Su(fu) mutation has a minimal phenotype, and we show here that Ci transcriptional activity in large part is regulated independently of Su(fu) by other pathway components. Mutant mice lacking Sufu in contrast show excessive pathway activity and die as embryos with patterning defects. Here we show that in cultured cells Hh stimulation can augment transcriptional activity of a Gli2 variant lacking Sufu interaction and, surprisingly, that regulation of Hh pathway targets is nearly normal in the neural tube of Sufu-/- mutant embryos that also lack Gli1 function. Some degree of Hh-induced transcriptional activation of Ci/Gli thus can occur independently of Sufu in both flies and mammals. We further note that Sufu loss can also reduce Hh induction of high-threshold neural tube fates, such as floor plate, suggesting a possible positive pathway role for Sufu.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Drosophila
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Hedgehog Proteins / genetics
Hedgehog Proteins / metabolism*
Kinesins / genetics
Kinesins / metabolism
Mice
Mice, Mutant Strains
Oncogene Proteins / genetics
Oncogene Proteins / metabolism*
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Signal Transduction / genetics
Signal Transduction / physiology
Trans-Activators / genetics
Trans-Activators / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*
Zinc Finger Protein GLI1

Substances

DNA-Binding Proteins
Drosophila Proteins
Hedgehog Proteins
Oncogene Proteins
Repressor Proteins
Su(fu) protein, Drosophila
Trans-Activators
Transcription Factors
Zinc Finger Protein GLI1
ci protein, Drosophila
cos protein, Drosophila
fu protein, Drosophila
Protein Serine-Threonine Kinases
Kinesins

Abstract

Publication types

MeSH terms

Substances

Grants and funding