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An Elk transcription factor is required for Runx-dependent survival signaling in the sea urchin embryo
- Source :
- Developmental Biology. 416:173-186
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Elk proteins are Ets family transcription factors that regulate cell proliferation, survival, and differentiation in response to ERK (extracellular-signal regulated kinase)-mediated phosphorylation. Here we report the embryonic expression and function of Sp-Elk, the single Elk gene of the sea urchin Strongylocentrotus purpuratus. Sp-Elk is zygotically expressed throughout the embryo beginning at late cleavage stage, with peak expression occurring at blastula stage. Morpholino antisense-mediated knockdown of Sp-Elk causes blastula-stage developmental arrest and embryo disintegration due to apoptosis, a phenotype that is rescued by wild-type Elk mRNA. Development is also rescued by Elk mRNA encoding a serine to aspartic acid substitution (S402D) that mimics ERK-mediated phosphorylation of a conserved site that enhances DNA binding, but not by Elk mRNA encoding an alanine substitution at the same site (S402A). This demonstrates both that the apoptotic phenotype of the morphants is specifically caused by Elk depletion, and that phosphorylation of serine 402 of Sp-Elk is critical for its anti-apoptotic function. Knockdown of Sp-Elk results in under-expression of several regulatory genes involved in cell fate specification, cell cycle control, and survival signaling, including the transcriptional regulator Sp-Runt-1 and its target Sp-PKC1, both of which were shown previously to be required for cell survival during embryogenesis. Both Sp-Runt-1 and Sp-PKC1 have sequences upstream of their transcription start sites that specifically bind Sp-Elk. These results indicate that Sp-Elk is the signal-dependent activator of a feed-forward gene regulatory circuit, consisting also of Sp-Runt-1 and Sp-PKC1, which actively suppresses apoptosis in the early embryo.
- Subjects :
- 0301 basic medicine
Sea urchin
Morpholino
Cell Survival
animal diseases
Embryonic Development
Apoptosis
Ternary Complex Factors
Biology
Article
Runx
03 medical and health sciences
fluids and secretions
0302 clinical medicine
Transcriptional regulation
Animals
Phosphorylation
PKC
Promoter Regions, Genetic
Molecular Biology
Transcription factor
Regulator gene
Genetics
Gene knockdown
Activator (genetics)
Core Binding Factor alpha Subunits
Gene Expression Regulation, Developmental
Cell Biology
Blastula
Oligonucleotides, Antisense
biology.organism_classification
Strongylocentrotus purpuratus
Cell biology
ERK
Elk
Embryo
Developmental Biology
030104 developmental biology
Gene Knockdown Techniques
Sea Urchins
030220 oncology & carcinogenesis
Signal Transduction
Subjects
Details
- ISSN :
- 00121606
- Volume :
- 416
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....45747ddb655dd32e9c4c79cde73a5840