Article Synopsis
- Neuronal transcription factors (TFs) like Cux1 are crucial for determining the function and connectivity of neurons, particularly in the development of corpus callosum projections.
- Cux1 regulates the expression of Kv1 potassium channels, which influence neuronal firing patterns; without Cux1, there’s a drop in Kv1 levels, leading to abnormal neuron activity and a loss of neural connections.
- The study highlights the interaction between genetic regulation and activity-dependent mechanisms in shaping brain circuits, emphasizing the role of firing patterns in neocortex development.
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Article Abstract
Neuronal subtype-specific transcription factors (TFs) instruct key features of neuronal function and connectivity. Activity-dependent mechanisms also contribute to wiring and circuit assembly, but whether and how they relate to TF-directed neuronal differentiation is poorly investigated. Here we demonstrate that the TF Cux1 controls the formation of the layer II/III corpus callosum (CC) projections through the developmental transcriptional regulation of Kv1 voltage-dependent potassium channels and the resulting postnatal switch to a Kv1-dependent firing mode. Loss of Cux1 function led to a decrease in the expression of Kv1 transcripts, aberrant firing responses, and selective loss of CC contralateral innervation. Firing and innervation were rescued by re-expression of Kv1 or postnatal reactivation of Cux1. Knocking down Kv1 mimicked Cux1-mediated CC axonal loss. These findings reveal that activity-dependent processes are central bona fide components of neuronal TF-differentiation programs and establish the importance of intrinsic firing modes in circuit assembly within the neocortex.
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| http://dx.doi.org/10.1016/j.neuron.2015.12.020 | DOI Listing |
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