PUBLICATION
Repression of Puma by Scratch2 is required for neuronal survival during embryonic development
- Authors
- Rodríguez-Aznar, E., and Nieto, M.A.
- ID
- ZDB-PUB-110124-18
- Date
- 2011
- Source
- Cell death and differentiation 18(7): 1196-207 (Journal)
- Registered Authors
- Nieto, Angela, Rodríguez-Aznar, Eva
- Keywords
- scratch, p53, puma, spinal cord, neuronal death, compensatory proliferation
- MeSH Terms
-
- Animals
- Apoptosis Regulatory Proteins/metabolism*
- DNA Damage
- Embryonic Development
- Gene Knockdown Techniques
- Nervous System/embryology
- Neurons/cytology
- Neurons/metabolism*
- Proto-Oncogene Proteins/metabolism*
- Transcription Factors/antagonists & inhibitors
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Tumor Suppressor Protein p53/antagonists & inhibitors
- Tumor Suppressor Protein p53/metabolism
- Zebrafish/embryology
- Zebrafish/metabolism
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 21252910 Full text @ Cell Death Differ.
Citation
Rodríguez-Aznar, E., and Nieto, M.A. (2011) Repression of Puma by Scratch2 is required for neuronal survival during embryonic development. Cell death and differentiation. 18(7):1196-207.
Abstract
Although Snail factors promote cell survival in development and cancer, the tumor-suppressor p53 promotes apoptosis in response to stress. p53 and Snail2 act antagonistically to regulate p53 upregulated modulator of apoptosis (Puma) and cell death in hematopoietic progenitors following DNA damage. Here, we show that this relationship is conserved in the developing nervous system in which Snail genes are excluded from vertebrate neurons and they are substituted by Scratch, a related but independent neural-specific factor. The transcription of scratch2 is induced directly by p53 after DNA damage to repress puma, thereby antagonizing p53-mediated apoptosis. In addition, we show that scratch2 is required for newly differentiated neurons to survive by maintaining Puma levels low during normal embryonic development in the absence of damage. scratch2 knockdown in zebrafish embryos leads to neuronal death through the activation of the intrinsic and extrinsic apoptotic pathways. To compensate for neuronal loss, the proliferation of neuronal precursors increases in scratch2-deficient embryos, reminiscent of the activation of progenitor/stem cell proliferation after damage-induced apoptosis. Our data indicate that the regulatory loop linking p53/Puma with Scratch is active in the vertebrate nervous system, not only controlling cell death in response to damage but also during normal embryonic development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping