PMID: 8598293Mar 15, 1996Paper

Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo

Genes & Development
M HammerschmidtA P McMahon

Abstract

Midline signaling by Hedgehog (Hh) family members has been implicated in patterning the vertebrate embryo. We have explored the potential regulatory role of cAMP-dependent protein kinase A (PKA) in these events. Zebrafish embryos injected with RNAs encoding Sonic hedgehog (Shh), Indian hedgehog (Ihh), or a dominant-negative regulatory subunit of PKA, PKI, have equivalent phenotypes. These include the expansion of proximal fates in the eye, ventral fates in the brain, and adaxial fates in somites and head mesenchyme. Moreover, ectopic expression of PKI partially rescues somite and optic stalk defects in no tail and cyclops mutants that lack midline structures that normally synthesize Shh. Conversely, all cell types promoted by ectopic expression of hhs and PKI are suppressed in embryos injected with RNA encoding a constitutively active catalytic subunit of PKA (PKA*). These results, together with epistasis studies on the block of ectopic Hh signaling by PKA*, indicate that PKA acts in target cells as a common negative regulator of Hedgehog signaling.

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Citations

Sep 23, 1997·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·E DahlR Balling
Feb 28, 2003·Developmental Biology·Wiebke HerzogMatthias Hammerschmidt
Jan 30, 2002·Trends in Neurosciences·Elisa Martí, Paola Bovolenta
Jan 1, 1997·Trends in Neurosciences·R O KarlstromF Bonhoeffer
Jun 17, 1999·Trends in Neurosciences·J S Eisen
Jan 1, 1997·Trends in Genetics : TIG·M HammerschmidtA P McMahon
Jul 26, 2003·Progress in Neurobiology·Katharine E Lewis, Judith S Eisen
May 30, 2001·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·G M KellyS Mangos
Feb 1, 1997·Current Opinion in Neurobiology·A F Schier
Nov 1, 1996·Nature Genetics·E RoesslerM Muenke
Oct 24, 2002·Development, Growth & Differentiation·Maureen A BrandonGregory J Podgorski
Apr 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kit Man TsangConstantine A Stratakis
Sep 26, 2008·Molecular Biology of the Cell·Melanie PhilippMarc G Caron
Sep 26, 1997·Genes & Development·C S BlagdenS M Hughes
Oct 18, 2006·Genes & Development·Jin Woo Kim, Greg Lemke
Jul 18, 2002·Annals of the New York Academy of Sciences·Paul S Amieux, G Stanley McKnight
Feb 16, 2010·Molecular and Cellular Biology·Xiaohui WenSuzie J Scales
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May 23, 2007·BMC Developmental Biology·Shang-Wei ChongVladimir Korzh
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