Summary
Pax6 is a well-known regulator of early neuroepithelial progenitor development. We discovered that it can also influence the later morphological and functional development of neurons in the prethalamus, which are unusual in retaining Pax6 expression as they mature. We used conditional mutagenesis to induce Pax6 loss-of-function mutations in prethalamic neurons and found that they showed developmental abnormalities when grown in vitro. Their rates of neurite elongation were disturbed and their axon initial segments were longer and extended further away from the soma than their control counterparts. They exhibited altered electrophysiological properties, including abnormal action potential (AP) waveforms and enhanced excitability, with abnormally low levels of current stimulus able to initiate APs. Our results significantly broaden the known functions of Pax6, suggesting that it has direct cell autonomous effects on the structural and functional development of some neurons. They provide new insights into the genetic regulation of the later stages of neurodevelopment.
Competing Interest Statement
The authors have declared no competing interest.