Speakers - 2026

Title: Role of Proteoglycans in Human Fetal Brain Development and Cerebral Malformations

Abstract

Proteoglycans (previously mucopolysaccharides) are carbohydrate/protein conjugates, synthesized and secreted into the cerebral extracellular space by astrocytes. The principal proteoglycans in human fetal brain are keratan sulfate (KS) and chondroitin sulfate, of similar molecular structure. KS forms a biochemical template in neuroblast migratory pathways to the cortical plate and axonal fascicles of the forebrain, expressed before neuroblasts migrate and before axons enter preformed fascicles such as the internal capsule. KS explains tangential neuroblast migratory guidance in absence of structural scaffolds such as radial glia, as a biochemical attractant of GABAergic cells. Extracellular KS granules adhere to neuronal membranes except dendritic spines; they recognize and repel glutamatergic and facilitate GABAergic axons even before axons contain neurotransmitter, thus regulating the excitatory/inhibitory ratio of neurons. In some malformations (holoprosencephaly) KS envelops individual axons excessively and may alter depolarization thresholds and epileptogenesis. KS immunoreactivity is early and intense in the globus pallidus, thalamus and amygdala. KS is not expressed in most posterior fossa structures including cranial nerves, cerebellum and brainstem nuclei including the cerebellar system except the basis pontis. KS does not envelop commissures including the corpus callosum or longitudinal ascending or descending tracts of the brainstem. Though not expressed in cerebellar cortex, KS forms transitory paired longitudinal septa between vermis and hemispheres, reminiscent of its presence in septa between neuromeres during neural tube segmentation, secreted by notochordal cells. Proteoglycans are a recently recognized factor in cerebral morphogenesis and participate in pathogenesis of malformations such as transmantle dysplasias.

Proteoglycans have clinical implications postnatally for seizure thresholds, developmental delay, intellectual impairment and motor deficits, hence the topic appears to fit the theme of this symposium. I hope that your scientific organizing committee may agree.