A role for Cajal–Retzius cells and reelin in the development of hippocampal connections

Abstract

During development of the nervous system, specific recognition molecules provide the cues necessary for the formation of neural connections. In some regions, guiding cues for axonal pathfinding and target selection are provided by specific cells that exist only transiently during development, such as the floorplate or the cortical subplate. In the hippocampus, distinct groups of fibres innervate different layers. We have tested the hypothesis that transient neurons in the hippocampus provide positional information for the targeting of these fibres. Here we report that ablation of Cajal-Retzius cells in organotypic slice cultures of hippocampus prevented the ingrowth of entorhinal but not of commissural afferents. Experiments inhibiting Reelin (an extracellular matrix protein expressed by Cajal-Retzius cells) and analysis of reeler mutant mice showed dramatic abnormalities in the development of entorhinal afferents. Thus Cajal-Retzius cells and reelin are essential for the formation of layer-specific hippocampal connections.

Mutant mice with scrambled brains: understanding the signaling pathways that control cell positioning in the CNS

“…After binding to lipoprotein receptors on the cell surface, Reln is internalized into vesicles. Binding of Reln to the receptors is inhibited by mAb CR-50, which blocks Reln function in vivo and in vitro (D'Arcangelo et al 1995(D'Arcangelo et al , 1999Ogawa et al 1995;Del Rio et al 1997;Nakajima et al 1997). These findings imply that Reln is a physiological ligand for lipoprotein receptors in the brain.…”

“…Reln is involved in the elaboration of entorhinal projections as they enter the hippocampus in postnatal mice (Del Rio et al 1997). Although the majority of Cajal-Retzius cells are lost during postnatal development of the cerebral cortex, resulting in reduced expression of Reln in the marginal zone, many cortical neurons that express ␥-aminobutyric acid as their primary neurotransmitter also express Reln (Alcantara et al 1998;Pesold et al 1998;Super et al 1998).…”

Modulation of dendritic differentiation by corticotropin-releasing factor in the developing hippocampus

“…Because lack of reelin causes perturbation of cortical lamination (14), control of neuronal positioning has been considered the major function of CR cells. However, recent results suggest additional roles for CR cells that are independent of reelin (15)(16)(17)(18).…”

Regenerating cortical connections in a dish: the entorhino-hippocampal organotypic slice co-culture as tool for pharmacological screening of molecules promoting axon regeneration

“…We and others have demonstrated the proper formation of the EHC in vitro 8,24,25,[36][37][38] . Anterograde labeling with Biocytin or TaueGFP cultures (Suppl.…”

“…Biocytin (biotinyl-lisine) is a powerful anterograde tracer in the mammalian central nervous system 35 . As indicated above, we and others have used Biocytin to trace the EHC in MCINN 24,36,37 . In the following paragraphs we briefly indicate the most important steps of the protocol.…”