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Pax-6 is required for thalamocortical pathway formation in fetal rats
1Department of Anatomy, School of Medicine, Keio University, Tokyo, Japan. hkawano@tmin.ac.jp
Insights
Pax-6 gene mutations disrupt thalamocortical pathway development in rats. Pax-6 expressing cells guide dorsal thalamic axons, crucial for normal brain wiring.
Area of Science:
- Developmental Neuroscience
- Neurobiology
- Genetics
Background:
- Pax-6 is a crucial transcription factor for eye, nose, and brain development.
- Mutations in Pax-6 are linked to developmental abnormalities in various species.
- The role of Pax-6 in establishing specific neural pathways, like the thalamocortical system, requires further investigation.
Purpose of the Study:
- To investigate the role of the Pax-6 gene in the formation of cerebral cortex afferent and efferent pathways.
- To analyze the specific impact of a Pax-6 mutation on thalamocortical axon pathfinding using the rat Small eye (rSey2) model.
Main Methods:
- Utilized the rat Small eye (rSey2) model with a Pax-6 gene mutation.
- Employed immunohistochemistry for neuronal cell adhesion molecules (TAG-1, L1) and neurofilaments.
- Applied DiI labeling from the cortical surface and dorsal thalamus to trace axonal trajectories.
Main Results:
- Cortical efferent axon development was normal in rSey2/rSey2 fetuses within the cortical anlage.
- Significant trajectory disorders were observed in dorsal thalamic axons in mutant fetuses.
- Unlike normal rats, mutant dorsal thalamic axons converged ventrolaterally and failed to reach the cortical anlage.
Conclusions:
- Pax-6 plays a critical role in guiding dorsal thalamic axons during thalamocortical pathway formation.
- Pax-6-expressing cell clusters in the ventral thalamus and amygdala are essential for correct axonal pathfinding.
- Disruption of Pax-6 function leads to aberrant thalamocortical connections, impacting brain development.
Abstract:
Pax-6, a transcription regulatory factor, has been demonstrated to play important roles in eye, nose, and brain development by analyzing mice, rats, and humans with a Pax-6 gene mutation. We examined the role of Pax-6 with special attention to the formation of efferent and afferent pathways of the cerebral cortex by using the rat Small eye (rSey2), which has a mutation in the Pax-6 gene. In rSey2/rSey2 fetuses, cortical efferent axons develop with normal trajectory, at least within the cortical anlage, when examined with immunohistochemistry of the neuronal cell adhesion molecule TAG-1 and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) labeling from the cortical surface. A remarkable disorder was found in the trajectory of dorsal thalamic axons by immunostaining of the neurofilament and the neural cell adhesion molecule L1 and DiI labeling from the dorsal thalamus. In normal rat fetuses, dorsal thalamic axons curved laterally in the ventral thalamus without invading a Pax-6-immunoreactive cell cluster in the ventral part of the ventral thalamus. These axons then coursed up to the cortical anlage, passing just dorsal to another Pax-6-immunoreactive cell cluster in the amygdaloid region. In contrast, in rSey2/rSey2 fetuses, dorsal thalamic axons extended downward to converge in the ventrolateral corner of the ventral thalamus and fanned out in the amygdaloid region without reaching the cortical anlage. These results suggest that Pax-6-expressing cell clusters along the thalamocortical pathway (ventral part of the ventral thalamus and amygdala) are responsible for the determination of the axonal pathfinding of the thalamocortical pathway.