PUBLICATION
Inhibition of protocadherin-alpha function results in neuronal death in the developing zebrafish
- Authors
- Emond, M.R., and Jontes, J.D.
- ID
- ZDB-PUB-080714-4
- Date
- 2008
- Source
- Developmental Biology 321(1): 175-187 (Journal)
- Registered Authors
- Emond, Michelle, Jontes, James
- Keywords
- zebrafish, protocadherin, apoptosis, imaging, in vivo
- MeSH Terms
-
- Animals
- Cadherins/chemistry
- Cadherins/genetics
- Cadherins/metabolism*
- Cell Death
- Central Nervous System/cytology
- Central Nervous System/embryology
- Embryo, Nonmammalian/metabolism
- Neurons/cytology*
- Protein Structure, Tertiary
- Zebrafish/embryology*
- Zebrafish/metabolism
- PubMed
- 18602383 Full text @ Dev. Biol.
Citation
Emond, M.R., and Jontes, J.D. (2008) Inhibition of protocadherin-alpha function results in neuronal death in the developing zebrafish. Developmental Biology. 321(1):175-187.
Abstract
The pcdhalpha/CNR gene comprises a diverse array of neuronal cell-surface proteins of the cadherin superfamily, although very little is known about their role in neural development. Here we provide the first in-depth characterization of pcdh1alpha in zebrafish. Whole-mount immunocytochemistry demonstrates that a large proportion of endogenous cytoplasmic domain immunoreactivity is present in the nucleus, suggesting that endoproteolytic cleavage and nuclear translocation of the intracellular domain are important aspects of pcdh1alpha activity in vivo. Using whole-mount immunocytochemistry and BAC-based expression of Pcdh1alpha-GFP fusion proteins, we find that Pcdh1alpha does not appear to form stable, synaptic puncta at early stages of synaptogenesis. We also demonstrate that the presence of the Pcdh1alpha cytoplasmic domain is essential for normal function. Truncation of Pcdh1alpha proteins, using splice-blocking antisense morpholinos to prevent the addition of the common intracellular domain to the entire pcdh1alpha cluster, results in neuronal apoptosis throughout the developing brain and spinal cord, demonstrating an essential role for pcdh1alpha in early neural development. This cell death phenotype can be attenuated by the expression of a soluble Pcdh1alpha cytoplasmic domain.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping