PUBLICATION

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

Authors
Hammerschmidt, M., Bitgood, M.J., and McMahon, A.P.
ID
ZDB-PUB-961014-392
Date
1996
Source
Genes & Development   10: 647-658 (Journal)
Registered Authors
Hammerschmidt, Matthias, McMahon, Andrew
Keywords
none
MeSH Terms
  • RNA/genetics
  • RNA/metabolism
  • Hedgehog Proteins
  • Animals
  • Proteins/genetics
  • Proteins/metabolism*
  • Gene Expression Regulation, Developmental
  • Central Nervous System/embryology
  • Trans-Activators*
  • Embryonic Development*
  • Eye/embryology
  • Cloning, Molecular
  • Phenotype
  • Zebrafish/embryology
  • Signal Transduction*
  • Mutation/genetics
  • Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases/genetics
  • Cyclic AMP-Dependent Protein Kinases/metabolism*
  • Gene Transfer Techniques
  • Embryonic Induction*
  • Epistasis, Genetic
(all 22)
PubMed
8598293 Full text @ Genes & Dev.
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.
Genes / Markers
Figures
No images available
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Marker Marker Type Name
dnPKAEFGdnPKA
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Mapping