Identification of Tbr-1/CASK complex target genes in neurons

Wang, Ting‐Fang; Ding, Chia‐Nung; Wang, Guey‐Shin; Luo, Shih‐Chi; Lin, Yi‐Ling; Ruan, Youlin; Hevner, Robert; Rubenstein, John L. R.; Hsueh, Yi‐Ping

doi:10.1111/j.1471-4159.2004.02845.x

Cited by 83Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeurogenesis and neuroplasticity mechanisms

Identification of Tbr-1/CASK complex target genes in neurons

Wang, Ting‐Fang, Ding, Chia‐Nung, Wang, Guey‐Shin, Luo, Shih‐Chi, Lin, Yi‐Ling, Ruan, Youlin, Hevner, Robert, Rubenstein, John L. R. +1 more·2004·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2004.02845.x

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Abstract

Tbr‐1, a neuron‐specific T‐box transcription factor, plays a critical role in brain development. Here, we performed a computational search using the non‐palindromic T‐box binding sequence, namely the non‐palindromic T‐element, to determine the putative downstream target genes of Tbr‐1. More than 20 identified genes containing the non‐palindromic T‐element in the 5′ regulatory region were found expressed in brain. Luciferase reporter assays using cultured hippocampal neurons showed that overexpression of Tbr‐1 and CASK‐enhanced promoter activities of some of these putative target genes, including NMDAR subunit 2b (NR2b), glycine transporter, interleukin 7 receptor (IL‐7R) and OX‐2. Among these genes, NR2b promoter responded strongest to overexpression of Tbr‐1 and CASK. Deletion of the non‐palindromic T‐elements from NR2b promoter impaired the induction by Tbr‐1 and CASK. We also examined expression of these target genes in Tbr‐1 knockout mice, it was found that NR2b expression was consistently downregulated. Similarly, both RNA and protein expression levels of NMDAR subunit 1 (NR1), which also contains the non‐palindromic T‐elements in its 5′ regulatory region, were reduced in Tbr‐1 knockout mice. We suggest that Tbr‐1/CASK protein complex regulates expression of these downstream target genes and thus modulates neuronal activity and function.

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With TBR1, CASK transcriptionally activates neurodevelopmental genes such as RELN.
“In conjunction with TBR1, CASK also transcriptionally activates several known neurodevelopmental genes, such as RELN (reelin), a gene with critical roles in neuronal development, synaptogenesis, and plasticity [79].”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [79]

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Authors: Wang, T., Ding, C., Wang, G., Luo, S., Lin, Y., Ruan, Y., Hevner, R., Rubenstein, J. L. R., & Hsueh, Y.
Affiliations: Institute of Biological Chemistry, Academia Sinica (TW)
Institute of Molecular Biology, Academia Sinica (TW)
University of California, San Francisco (US)
University of Washington (US)
Corresponding author: Hsueh, Yi‐Ping
ORCID: Wang, Ting‐Fang
Wang, Guey‐Shin
Luo, Shih‐Chi
Lin, Yi‐Ling
Hevner, Robert
Rubenstein, John L. R.
Hsueh, Yi‐Ping
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2004-12
Volume: 91
Issue: 6
Pages: 1483-1492
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2004.02845.x
OpenAlex: W1898303357
Cited by: 83
References: 35
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 9 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 3 · 2017: 2 · 2016: 8 · 2015: 2 · 2014: 3
FWCI: 1.76
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1 d)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Council
Academia Sinica
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: CASK, T-box transcription factor, transcription factor target genes, NR2B, NMDA receptor subunit 2B, NR1, glycine transporter, CD127, hippocampal neurons, brain development, gene expression regulation
MeSH terms: Animals, Antigens, Surface, Base Sequence, Cells, Cultured, Chlorocebus aethiops, DNA-Binding Proteins, Embryo, Mammalian, Gene Expression Regulation, Hippocampus, Humans, Molecular Sequence Data, Neurons, Promoter Regions, Genetic, Antigens, CD, Receptors, N-Methyl-D-Aspartate, Calcium-Calmodulin-Dependent Protein Kinases, Mice, Knockout, COS Cells, Receptors, Interleukin-7, T-Box Domain Proteins, Amino Acid Transport Systems, Neutral, Glycine Plasma Membrane Transport Proteins, Mice, Rats, Guanylate Kinases

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Identification of Tbr-1/CASK complex target genes in neurons

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