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
-
- Animals
- Central Nervous System/embryology
- Cloning, Molecular
- Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors
- Cyclic AMP-Dependent Protein Kinases/genetics
- Cyclic AMP-Dependent Protein Kinases/metabolism*
- Embryonic Development*
- Embryonic Induction*
- Epistasis, Genetic
- Eye/embryology
- Gene Expression Regulation, Developmental
- Gene Transfer Techniques
- Hedgehog Proteins
- Mutation/genetics
- Phenotype
- Proteins/genetics
- Proteins/metabolism*
- RNA/genetics
- RNA/metabolism
- Signal Transduction*
- Trans-Activators*
- Zebrafish/embryology
- PubMed
- 8598293 Full text @ Genes & Dev.
Citation
Hammerschmidt, M., Bitgood, M.J., and McMahon, A.P. (1996) Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo. Genes & Development. 10:647-658.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping