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BMC Genomics. 2015 Jul 24;16:545. doi: 10.1186/s12864-015-1770-3.

Combined serial analysis of gene expression and transcription factor binding site prediction identifies novel-candidate-target genes of Nr2e1 in neocortex development.

Author information

1
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. jean-francois.schmouth@mail.mcgill.ca.
2
Genetics Graduate Program, University of British Columbia, Vancouver, BC, V6T 1Z2, Canada. jean-francois.schmouth@mail.mcgill.ca.
3
Current address: Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, H3A 2B4, Canada. jean-francois.schmouth@mail.mcgill.ca.
4
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. dave@cmmt.ubc.ca.
5
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. ximena@cmmt.ubc.ca.
6
Genetics Graduate Program, University of British Columbia, Vancouver, BC, V6T 1Z2, Canada. ximena@cmmt.ubc.ca.
7
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. yyxie@cmmt.ubc.ca.
8
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. slavita@gmail.com.
9
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. kbanks@cmmt.ubc.ca.
10
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. rbonaguro@cmmt.ubc.ca.
11
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. wongsia@gmail.com.
12
Genetics Graduate Program, University of British Columbia, Vancouver, BC, V6T 1Z2, Canada. sjones@bcgsc.ca.
13
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 4S6, Canada. sjones@bcgsc.ca.
14
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada. sjones@bcgsc.ca.
15
Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. sjones@bcgsc.ca.
16
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 4S6, Canada. mmarra@bcgsc.ca.
17
Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. mmarra@bcgsc.ca.
18
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. simpson@cmmt.ubc.ca.
19
Genetics Graduate Program, University of British Columbia, Vancouver, BC, V6T 1Z2, Canada. simpson@cmmt.ubc.ca.
20
Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. simpson@cmmt.ubc.ca.
21
Department of Psychiatry, University of British Columbia, Vancouver, BC, V6T 2A1, Canada. simpson@cmmt.ubc.ca.
22
Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. wyeth@cmmt.ubc.ca.
23
Genetics Graduate Program, University of British Columbia, Vancouver, BC, V6T 1Z2, Canada. wyeth@cmmt.ubc.ca.
24
Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. wyeth@cmmt.ubc.ca.

Abstract

BACKGROUND:

Nr2e1 (nuclear receptor subfamily 2, group e, member 1) encodes a transcription factor important in neocortex development. Previous work has shown that nuclear receptors can have hundreds of target genes, and bind more than 300 co-interacting proteins. However, recognition of the critical role of Nr2e1 in neural stem cells and neocortex development is relatively recent, thus the molecular mechanisms involved for this nuclear receptor are only beginning to be understood. Serial analysis of gene expression (SAGE), has given researchers both qualitative and quantitative information pertaining to biological processes. Thus, in this work, six LongSAGE mouse libraries were generated from laser microdissected tissue samples of dorsal VZ/SVZ (ventricular zone and subventricular zone) from the telencephalon of wild-type (Wt) and Nr2e1-null embryos at the critical development ages E13.5, E15.5, and E17.5. We then used a novel approach, implementing multiple computational methods followed by biological validation to further our understanding of Nr2e1 in neocortex development.

RESULTS:

In this work, we have generated a list of 1279 genes that are differentially expressed in response to altered Nr2e1 expression during in vivo neocortex development. We have refined this list to 64 candidate direct-targets of NR2E1. Our data suggested distinct roles for Nr2e1 during different neocortex developmental stages. Most importantly, our results suggest a possible novel pathway by which Nr2e1 regulates neurogenesis, which includes Lhx2 as one of the candidate direct-target genes, and SOX9 as a co-interactor.

CONCLUSIONS:

In conclusion, we have provided new candidate interacting partners and numerous well-developed testable hypotheses for understanding the pathways by which Nr2e1 functions to regulate neocortex development.

PMID:
26204903
PMCID:
PMC4512088
DOI:
10.1186/s12864-015-1770-3
[Indexed for MEDLINE]
Free PMC Article

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