Using in situ hybridization, expression of the mRNA for reelin, the ge
ne most probably responsible for the reeler trait, was studied during
mouse brain development, from embryonic day 13 to maturity. The highes
t revel of expression was found in Cajal-Retzius neurons, while a high
signal was also seen in the olfactory bulb, the external granular lay
er of the cerebellum and, particularly at early developmental stages,
in hypothalamic differentiation fields, tectum and spinal cord. A mode
rate to low level of expression was found in the septal area, striatal
fields, habenular nuclei, some thalamic nuclei, particularly the late
ral geniculate, the retina and some nuclei of the reticular formation
in the central field of the medulla. Paradoxically, no reelin expressi
on was detected in radial glial cells, the cortical plate, Purkinje ce
lls, inferior olivary neurons and many other areas that are characteri
stically abnormal in reeler mutant mice. Together with other prelimina
ry studies, the present observations suggest that the action of reelin
is indirect, possibly mediated by the extracellular matrix. Most of t
he data can be explained by supposing that reelin is a cell-repulsive
molecule which prevents migrating neurons from invading reelin-rich ar
eas, and thus facilitates the deployment of radial glial cell processe
s and the formation of early architectonic patterns.