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TCF7L2 regulates postmitotic differentiation programmes and excitability patterns in the thalamus
Marcin Andrzej Lipiec1,2, Joanna Bem1, Kamil Koziński1
1Centre of New Technologies, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
Development (Cambridge, England)
|July 18, 2020
Summary
Transcription factor TCF7L2 acts as a master regulator in the vertebrate brain, controlling neuronal development and function. This study demonstrates its crucial role in thalamic terminal selection and neuronal differentiation.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Terminal selector transcription factors (TSTFs) are known to control neuronal phenotypes in invertebrates.
- However, their roles in vertebrate brains, particularly in the thalamus, remain largely unexplored.
- Identifying TSTFs is crucial for understanding neuronal differentiation and connectivity.
Purpose of the Study:
- To investigate the role of TCF7L2 as a thalamic terminal selector.
- To determine if TCF7L2 regulates distinct stages of postmitotic differentiation in the thalamus.
- To elucidate the function of TCF7L2 in neuronal connectivity and electrophysiological properties.
Main Methods:
- Utilized complete and conditional knockout mouse models for Tcf7l2.
- Analyzed neuronal connectivity and clustering in the thalamo-habenular region.
- Examined gene expression patterns, including subregional transcription factors and cell migration/axon guidance genes.
- Assessed electrophysiological features of thalamic neurons in mutant mice.
Main Results:
- Tcf7l2 knockout embryos exhibited disrupted neuronal connectivity and clustering in the thalamo-habenular region.
- Loss of subregional thalamic and habenular transcription factors and downregulation of region-specific genes were observed.
- Postnatal Tcf7l2 knockout impaired the induction of genes responsible for thalamic electrophysiological features.
- TCF7L2 was identified as a direct regulator of many of these critical genes.
- Mutant mice showed impaired firing modes in thalamic neurons, confirming TCF7L2's role in terminal selection.
Conclusions:
- TCF7L2 functions as a critical thalamic terminal selector in vertebrates.
- It orchestrates stage-specific genetic programs during embryonic development and postnatal differentiation.
- TCF7L2 maintains regional transcriptional networks and induces terminal electrophysiological properties in thalamic neurons.
- These findings support the existence of master regulators in the vertebrate brain controlling neuronal development and function.
