Psychiatric risk gene Transcription Factor 4 (TCF4) regulates the density and connectivity of distinct inhibitory interneuron subtypes

Chen, Huei-Ying; Phan, BaDoi N.; Shim, Gina; Hamersky, Gregory R.; Sadowski, Norah; O’Donnell, Thomas S.; Sripathy, Srinidhi Rao; Bohlen, Joseph F.; Pfenning, Andreas R.; Maher, Brady J.

doi:10.1038/s41380-023-02248-z

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Cited by 5 publications

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Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism

Espinoza,

Carrazana,

Retamal-Fredes

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism

Espinoza,

Carrazana,

Retamal-Fredes

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia

Zhang,

Wu,

Cheng

et al. 2024

Mol Psychiatry

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Tcf4Deficiency Causes Recurrent Seizures in Mice

Craciun,

DeNittis,

Davis

et al. 2024

Preprint

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Transcription factor 4 (TCF4) is a transcription factor that is critical for the normal development and function of the central nervous system. Haploinsufficiency of TCF4 causes Pitt-Hopkins Syndrome (PTHS), a lifelong neurodevelopmental disorder characterized by seizures and intellectual disability. To expand our currently limited understanding of TCF4 function and PTHS pathophysiology, we created a mouse model of PTHS with largely astrocyte-specific heterozygous knockout of Tcf4. These mice developed severe recurrent seizures and had decreased lifespans. In addition, we found that these mice had astrogliosis as well as increased neuronal activity in the cortex, hippocampus, amygdala, and hypothalamus. Furthermore, single nucleus RNA sequencing analysis revealed global changes in the gene expression profiles of excitatory neurons, inhibitory neurons, astrocytes, and oligodendrocytes of PTHS compared to wild-type mice. Overall, this is the first report of a PTHS mouse model with seizures, providing the field with a tool to investigate the mechanisms of PTHS development and progression and develop therapeutics for PTHS and its associated epilepsy.

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Psychiatric risk gene Transcription Factor 4 (TCF4) regulates the density and connectivity of distinct inhibitory interneuron subtypes

Cited by 5 publications

References 91 publications

Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism

Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism

Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia

Tcf4Deficiency Causes Recurrent Seizures in Mice

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