Pax-6 is required for thalamocortical pathway formation in fetal rats

Pax-6, a transcription regulatory factor, has been demonstrated to play imp ortant roles in eye, nose, and brain development by analyzing mice, rats, a nd humans with a Pax-6 gene mutation. We examined the role of Pax-6 with sp ecial attention to the formation of efferent and afferent pathways of the c erebral cortex by using the rat Small eye (rSey(2)), which has a mutation i n the Pax-6 gene. In rSey(2)/rSey(2) fetuses, cortical efferent axons devel op with normal trajectory, at least within the cortical anlage, when examin ed with immunohistochemistry of the neuronal cell adhesion molecule TAG-1 a nd 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 i n the ventral part of the ventral thalamus. These axons then coursed up to the cortical anlage, passing just dorsal to another Pax-6-immunoreactive ce ll cluster in the amygdaloid region. In contrast, in rSey2/rSey2 fetuses, d orsal thalamic axons extended downward to converge in the ventrolateral cor ner 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 ventra l thalamus and amygdala) are responsible for the determination of the axona l pathfinding of the thalamocortical pathway. J. Comp. Neurol. 408:147-160, 1999. (C) 1999 Wiley-Liss, Inc.