Cajal-Retzius cell ontogenesis and death in mouse brain visualized with horseradish peroxidase and electron microscopy.

The ontogenetic development of Cajal-Retzius cells was studied in mouse by local application of horseradish peroxidase over the developing neocortex, revelation with 3,3'-diaminobenzidene and examination from horizontal thick sections. Cajal-Retzius cells were completely stained in Golgi-like fashion. The Cajal-Retzius cells were seen to be elongated spindle-shaped bipolar neurons with their main processes horizontally oriented. They were exclusively located in the first cortical layer and were connected to the cortex surface by the numerous vertical appendages. Except for these appendages, the Cajal-Retzius cells were two-dimensional, with an immature structure at their tips resembling a growth cone. Cajal-Retzius cell dendrites were up to 400-microns-long and reached their maximal length prenatally. Their axon and its collaterals were very fine and sometimes measured several millimetres. It followed a random but planar trajectory confined to the first layer. Healthy Cajal-Retzius bearing growth cones were seen until one week after birth when signs of Cajal-Retzius cell degeneration began to occur and intensified in the days that followed. Rough endoplasmic reticulum and Golgi complex swelling along with a progressive darkening of the Cajal-Retzius cells were revealed by electron microscopy, strongly suggesting that most Cajal-Retzius cells disappear from the first cortical layer. Usually neuronal death is the result of cell deafferentation following synapse retraction; however, this effect does not seem to apply to Cajal-Retzius cells engaged in the process of death since normal synaptic junctions were seen on them. No signs of the morphological transformation of Cajal-Retzius cells into persisting horizontal first layer cells were observed. The concept of dual origin of neocortex is discussed in light of the similar fate of Cajal-Retzius cells and subplate neurons which both are transient neurons.