PUBLICATION

CoRest1 regulates neurogenesis in a stage-dependent manner

Authors

Monestime, C.M., Taibi, A., Gates, K.P., Jiang, K., Sirotkin, H.I.

ID

ZDB-PUB-190714-6

Date

2019

Source

Developmental Dynamics : an official publication of the American Association of Anatomists 248(10): 918-930 (Journal)

Registered Authors

Gates, Keith, Sirotkin, Howard

Keywords

CoRest1, Rest/NRSF, neurogenesis, zebrafish

MeSH Terms

Sin3 Histone Deacetylase and Corepressor Complex/metabolism
Animals
Zebrafish
Embryo, Nonmammalian
Mutant Proteins
Neurogenesis/drug effects*
Gastrula/physiology
Repressor Proteins/metabolism
Gene Expression Regulation, Developmental
Co-Repressor Proteins/genetics
Co-Repressor Proteins/physiology*

(all 11)

PubMed

31301200 Full text @ Dev. Dyn.

Abstract

Background Developmental processes, including neuronal differentiation, require precise regulation of transcription. The RE-1 silencing transcription factor (Rest), is often called a "master neuronal regulator" due to its large number of neural-specific targets. Rest recruits CoRest (Rcor) and Sin3 co-repressor complexes to gene regulatory sequences. CoRest not only associates with Rest, but with other transcription regulators. In this study, we generated zebrafish rcor1 mutants using transcription activator- like effector nucleases (TALENs), to study its requisite role in repression of Rest target genes as well as Rest-independent Rcor1 developmental functions.

Results While rcor1 mutants have a slight decrease in fitness, most survived and produced viable offspring. We examined expression levels of RE1-containing genes in Maternal Zygotic rcor1 mutants (MZrcor1) and found that Rcor1 is generally not required for repression of Rest target genes at early stages. However, MZrcor1 mutants undergo more rapid neurogenesis compared to controls. We found that at gastrula stages, Rcor1 acts as a repressor of her gene family, but at later stages, many of these genes were increased in the MZrcor1 mutant.

Conclusions Based on these findings, the central role of CoRest1 in neurogenesis is likely due to a Rest- independent role rather than as a Rest co-repressor. This article is protected by copyright. All rights reserved.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
rcor1^sbu54/sbu54	standard conditions	Sphere	whole organism amph expression decreased amount, abnormal	Fig. 3
rcor1^sbu54/sbu54	standard conditions	Sphere	whole organism gpr27 expression decreased amount, abnormal	Fig. 3
rcor1^sbu54/sbu54	standard conditions	Sphere	whole organism rcor2 expression decreased amount, abnormal	Fig. 3
rcor1^sbu54/sbu54	standard conditions	Sphere	whole organism rcor3 expression decreased amount, abnormal	Fig. 3
rcor1^sbu54/sbu54	standard conditions	Sphere	whole organism snap25b expression increased amount, abnormal	Fig. 3
rcor1^sbu54/sbu54	standard conditions	Shield	whole organism her1 expression increased amount, abnormal	Fig. 7
rcor1^sbu54/sbu54	standard conditions	Shield	whole organism her4.1 expression increased amount, abnormal	Fig. 7
rcor1^sbu54/sbu54	standard conditions	Shield	whole organism her6 expression increased amount, abnormal	Fig. 7
rcor1^sbu54/sbu54	standard conditions	5-9 somites	head elavl3 expression mislocalised, abnormal	Fig. 6
rcor1^sbu54/sbu54	standard conditions	5-9 somites	hindbrain neural rod neurog1 expression increased amount, abnormal	Fig. 8

1 - 10 of 31

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
rcor1	TALEN1-rcor1	TALEN

Fish

Fish
knu3Tg
rcor1^sbu51
rcor1^sbu52
rcor1^sbu53
rcor1^sbu54/sbu54
rcor1^sbu54/sbu54
rcor1^sbu54/sbu54; knu3Tg
rcor1^sbu55
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Monestime et al., 2019 ZDB-PUB-190714-6 PMID:31301200

CoRest1 regulates neurogenesis in a stage-dependent manner

Monestime et al., 2019

ZDB-PUB-190714-6
PMID:31301200