The embryonic development of the inferior olivary complex in normal and reeler (rlORL) mutant mice

Abstract

The development of the inferior olivary complex has been studied comparatively in normal and reeler mutant mice, from embryonic day 14 to birth. In both genotypes, cells migrate tangentially, from the lateral recess of the fourth ventricle, until they reach the ventral rhombencephalon where they enter the olive radially. Some cells also enter the olive laterally, from its external side. In both genotypes, olivary neurons differentiate following the same morphological sequence, both in terms of dendritic deployment and of axonal growth. Olivofugal axons cross the midline as early as E14. Synapses are rare in the inferior olivary complex during the prenatal period. Radial glial cells and the first stages of astrocytogenesis appear similar in both genotypes. The process of olivary maturation begins at E15. In normal embryos, this occurs concurrently with a subdivision of the olivary complex, clearly defined at birth: the principal olive (PO) is "U" shaped and located between the medial accessory olive (MAO) and the dorsal accessory olive (DAO). In reeler mutants, there are abnormalities in the configuration of the inferior olivary complex. Even the earliest lobulated contours are anomalous. The ultimate configuration, though containing the principal elements of the normal complex, is blunted, compact, and very much less "calligraphic" in its undulation than in the normal animal. The reeler dysplasia is mild at E15 and becomes increasingly evident at later developmental stages. These observations show that the reeler gene primarily affects the position of neuronal cells relative to other cellular elements and to fiber strata, while leaving relatively intact the phenomena of cell migration and differentiation. Afferent fibers from spinal and midbrain origin are probably involved in the division of the olivary complex into its components (Martin et al., '80). In addition, the development of the cerebellar cortex could influence the morphogenesis of the olivary nuclei. However, the architectonic malformation of the reeler inferior olive can hardly be exclusively attributed to perturbations of its hodological relationships. It is proposed that the abnormal development of the inferior olive in reeler mutants is largely dependent on a local, intrinsic action of the mutant gene on the olivary primordium.