The malformation of the cerebellar fissura prima: a tool for studying histogenetic processes.

ABSTRACT

Due to its regular cytoarchitecture and the relatively low number of cell types, the development of the cerebellar cortex is a model of election for studies of morphogenetic processes. To unravel the cellular and molecular mechanisms that regulate cell development, migration and differentiation and the settling of local circuits, pertubation of the three-layered organization of the cerebellar cortex has been induced by X-ray irradiation or antimitotic drug. In this review we deal with some data about the incidence and development of the malformation of the cerebellar fissura prima of the rat, as an eligible model for histogenetic studies. The naturally occurring malformation of the fissura prima is characterized by the loss of the three-layered organization of folia and the presence of large masses of ectopic granule cells. The malformation appears to be under genetic control, since the incidence of affected animals is consistent over extended breeding cycles, although the target of the eventual mutation is unknown. The observation of development of the malformation in infant rats suggests that a defect in meninges, and in particular in the pia mater, is a primary contributing factor. The molecules responsible for this defect are not identified, but they must be involved in basal lamina stabilization or destabilization. In fact, there is evidence that meninges do develop during first stages of histogenesis and only later degenerate. A possible correlation with certain human pathologies that involve defects in foliation is discussed.