Evidence map›Paper›PMID 34564703›Full record

SynthesisTranslational psychiatry2021

Adult brain neurons require continual expression of the schizophrenia-risk gene Tcf4 for structural and functional integrity.

Dipannita Sarkar, Mohammad Shariq, Deepanjali Dwivedi, Nirmal Krishnan, Ronald Naumann, Upinder Singh Bhalla, Hiyaa Singhee Ghosh

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 19 citations in OpenAlex.

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  9. Whole-brain analysis of CObioRxiv : the preprint server for biology · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Dipannita SarkarNational Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.
Mohammad ShariqNational Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.ORCID http://orcid.org/0000-0003-4766-6793
Deepanjali DwivediNational Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.ORCID http://orcid.org/0000-0001-9992-9167
Nirmal KrishnanNational Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.ORCID http://orcid.org/0000-0003-4321-1257
Ronald NaumannMPI of Molecular Cell Biology and Genetics, Dresden, 01307, Germany.ORCID http://orcid.org/0000-0003-2084-5150
Upinder Singh BhallaNational Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.ORCID http://orcid.org/0000-0003-1722-5188
Hiyaa Singhee GhoshNational Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India. hiyaa@ncbs.res.in.ORCID http://orcid.org/0000-0001-6224-1043
Tata Institute of Fundamental Research · INMax Planck Institute of Molecular Cell Biology and Genetics · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The schizophrenia-risk gene Tcf4 has been widely studied in the context of brain development using mouse models of haploinsufficiency, in utero knockdown and embryonic deletion. However, Tcf4 continues to be abundantly expressed in adult brain neurons where its functions remain unknown. Given the importance of Tcf4 in psychiatric diseases, we investigated its role in adult neurons using cell-specific deletion and genetic tracing in adult animals. Acute loss of Tcf4 in adult excitatory neurons in vivo caused hyperexcitability and increased dendritic complexity of neurons, effects that were distinct from previously observed effects in embryonic-deficiency models. Interestingly, transcriptomic analysis of genetically traced adult-deleted FACS-sorted Tcf4-knockout neurons revealed that Tcf4 targets in adult neurons are distinct from those in the embryonic brain. Meta-analysis of the adult-deleted neuronal transcriptome from our study with the existing datasets of embryonic Tcf4 deficiencies revealed plasma membrane and ciliary genes to underlie Tcf4-mediated structure-function regulation specifically in adult neurons. The profound changes both in the structure and excitability of adult neurons upon acute loss of Tcf4 indicates that proactive regulation of membrane-related processes underlies the functional and structural integrity of adult neurons. These findings not only provide insights for the functional relevance of continual expression of a psychiatric disease-risk gene in the adult brain but also identify previously unappreciated gene networks underpinning mature neuronal regulation during the adult lifespan.

Indexed as

SchizophreniaAnimalsBrainDisease Models, AnimalHaploinsufficiencyMiceNeurons

Identifiers

PMID34564703
PMCPMC8464606
OpenAlexW3204061000

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.