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Zbtb20 Defines a Hippocampal Neuronal Identity Through Direct Repression of Genes That Control Projection Neuron Development in the Isocortex
Abstract
Hippocampal pyramidal neurons are important for encoding and retrieval of spatial maps and episodic memories. While previous work has shown that Zbtb20 is a cell fate determinant for CA1 pyramidal neurons, the regulatory mechanisms governing this process are not known. In this study, we demonstrate that Zbtb20 binds to genes that control neuronal subtype specification in the developing isocortex, including Cux1, Cux2, Fezf2, Foxp2, Mef2c, Rorb, Satb2, Sox5, Tbr1, Tle4, and Zfpm2. We show that Zbtb20 represses these genes during ectopic CA1 pyramidal neuron development in transgenic mice. These data reveal a novel regulatory mechanism by which Zbtb20 suppresses the acquisition of an isocortical fate during archicortical neurogenesis to ensure commitment to a CA1 pyramidal neuron fate. We further show that the expression pattern of Zbtb20 is evolutionary conserved in the fetal human hippocampus, where it is complementary to the expression pattern of the Zbtb20 target gene Tbr1. Therefore, the disclosed Zbtb20-mediated transcriptional repressor mechanism may be involved in development of the human archicortex.
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“Specific marker genes for cluster 6 included RNA binding proteins (RBPs) Arpp21 and R3hdm1 (Figure S4, S5A, and Table S3) and several genes (Rorb, Cux1, Cux2, and Mef2c) that are typically repressed in hippocampal pyramidal neurons by Zbtb20 and are normally expressed within cortical neurons (Figure S4, S5B, and Table S3) (Nielsen et al., 2014; Rehfeld et al., 2018).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Nielsen et al., 2014
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Satb2 Regulates Callosal Projection Neuron Identity in the Developing Cerebral Cortex
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Lhx2 Selector Activity Specifies Cortical Identity and Suppresses Hippocampal Organizer Fate
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Metadata
- Authors
- Nielsen, J. V., Thomassen, M., Møllgård, K., Noraberg, J., & Jensen, N. A.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-01-02
- Volume
- 24
- Issue
- 5
- Pages
- 1216-1229
- ISSN
- 1460-2199
- 1047-3211
- Cited by
- 59
- References
- 10
- Language
- en
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