Keratan sulfate proteoglycan is not expressed in human fetal cerebellar system except pontine nuclei and transitory vermal septa or in fasciculi caudal to the internal capsule.

We determined spatial/temporal expression of keratan sulfate proteoglycan (KS) in the developing cerebellar system, fasciculi, and dysgeneses. KS is an extracellular molecule secreted by astrocytes that forms a template for neuroblastic migration and axonal fascicles and creates perineural nets. We studied KS immunoreactivity in cerebellar cortex, deep cerebellar, inferior olivary, red and pontine nuclei, and white matter of 25 control human fetuses 12-41 weeks gestation and 16 cerebellar dysgeneses. Dentate, inferior olivary, and red nuclei were nonreactive at all ages. Pontine nuclei were positive from the early second trimester. Bergmann glia and cerebellar white matter pathways were nonreactive throughout fetal and postnatal life. Transitory KS septa demarcated the vermal/hemispheric boundary. KS was not expressed in Dandy-Walker or Chiari malformations, cerebellar hypoplasia, heterotopia, pontocerebellar hypoplasia, or rhombencephalosynapsis. Axonal fascicles caudal to the internal capsule did not exhibit KS. The absence of hindbrain KS contrasts with strong forebrain immunoreactivity. Lack of KS expression in typically developing cerebellum and associated brainstem nuclei (except pontine), or in dysgeneses, implies that KS does not contribute to cerebellar system malformation pathogenesis. Transitory KS septa define early vermal margins similar to neuromeric segmentation septa. The intense KS template of the internal capsule does not extend caudally into brainstem fascicles.