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Published on: April 24, 2021
The C. elegans COE transcription factor UNC-3 activates lineage-specific apoptosis and affects neurite growth in the
Jinbo Wang1, Jyothsna Chitturi2, Qinglan Ge1
1State Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
Mechanisms that regulate apoptosis in a temporal and lineage-specific manner remain poorly understood. The COE (Collier/Olf/EBF) transcription factors have been implicated in the development of many cell types, including neurons. Here, we show that the sole Caenorhabditis elegans COE protein, UNC-3, together with a histone acetyltransferase, CBP-1/P300, specifies lineage-specific apoptosis and certain aspects of neurite trajectory. During embryogenesis, the RID progenitor cell gives rise to the RID neuron and RID sister cell; the latter undergoes apoptosis shortly after cell division upon expression of the pro-apoptotic gene egl-1. We observe UNC-3 expression in the RID progenitor, and the absence of UNC-3 results in the failure of the RID lineage to express a Pegl-1::GFP reporter and in the survival of the RID sister cell. Lastly, UNC-3 interacts with CBP-1, and cbp-1 mutants exhibit a similar RID phenotype to unc-3. Thus, in addition to playing a role in neuronal terminal differentiation, UNC-3 is a cell lineage-specific regulator of apoptosis.
Insights
The Collier/Olf/EBF (COE) transcription factor UNC-3 regulates programmed cell death in specific cell lineages. UNC-3, with CBP-1, controls apoptosis and neuronal development in Caenorhabditis elegans.
Area of Science:
- Developmental biology
- Neuroscience
- Cell biology
Background:
- Mechanisms of programmed cell death (apoptosis) in a temporal and lineage-specific manner are not fully understood.
- COE transcription factors are involved in the development of various cell types, including neurons.
Purpose of the Study:
- To investigate the role of the Caenorhabditis elegans COE protein UNC-3 in lineage-specific apoptosis and neuronal development.
- To elucidate the interaction between UNC-3 and CBP-1 in regulating these processes.
Main Methods:
- Analysis of UNC-3 expression in the RID progenitor cell during embryogenesis.
- Assessment of the RID lineage phenotype in unc-3 and cbp-1 mutants using a Pegl-1::GFP reporter.
- Investigation of UNC-3 and CBP-1 interaction.
Main Results:
- UNC-3 is expressed in the RID progenitor cell.
- Absence of UNC-3 leads to the failure of RID lineage to express Pegl-1::GFP and survival of the RID sister cell.
- UNC-3 interacts with CBP-1, and cbp-1 mutants show similar RID phenotypes to unc-3 mutants.
Conclusions:
- UNC-3 acts as a cell lineage-specific regulator of apoptosis.
- UNC-3, in conjunction with CBP-1, plays a role in specifying lineage-specific apoptosis and aspects of neurite trajectory.
- UNC-3 is involved in both neuronal terminal differentiation and programmed cell death regulation.
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