Pax6 loss alters the morphological and electrophysiological development of mouse prethalamic neurons

Abstract

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.

Pathophysiological Roles of Abnormal Axon Initial Segments in Neurodevelopmental Disorders

“…Another study found that, in mouse models of ASD, mice with mutations in the transcription factor PAX6 exhibited changes of AIS that were significantly further from the cell body and exhibited longer AnkG staining of prethalamic neurons [118].…”

Pathophysiological Roles of Abnormal Axon Initial Segments in Neurodevelopmental Disorders

“…Another study found that, in mouse models of ASD, mice with mutations in the transcription factor PAX6 exhibited changes of the AIS that were significantly further from the cell body and exhibited a longer AnkG staining of prethalamic neurons [118].…”