Cajal-Retzius neurons are required for the development of the human hippocampal fissure.
Date
2019Abstract
Cajal-Retzius neurons (CRN) are the main source of Reelin in the marginal zone of the developing neocortex
and hippocampus (HC). They also express the transcription factor p73 and are complemented by laterappearing GABAergic Reelin+ interneurons. The human dorsal HC forms at gestational week 10 (GW10), when
it develops a rudimentary Ammonic plate and incipient dentate migration, although the dorsal hippocampal
fissure (HF) remains shallow and contains few CRN. The dorsal HC transforms into the indusium griseum (IG),
concurrently with the rostro-caudal appearance of the corpus callosum, by GW14–17. Dorsal and ventral HC
merge at the site of the former caudal hem, which is located at the level of the future atrium of the lateral
ventricle and closely connected with the choroid plexus. The ventral HC forms at GW11 in the temporal lobe.
The ventral HF is wide open at GW14–16 and densely populated by large numbers of CRNs. These are in
intimate contact with the meninges and meningeal blood vessels, suggesting signalling through diverse
pathways. At GW17, the fissure deepens and begins to fuse, although it is still marked by p73/Reelin+ CRNs.
The p73KO mouse illustrates the importance of p73 in CRN for HF formation. In the mutant, Tbr1/Reelin+ CRNs
are born in the hem but do not leave it and subsequently disappear, so that the mutant cortex and HC lack
CRN from the onset of corticogenesis. The HF is absent, which leads to profound architectonic alterations of
the HC. To determine which p73 isoform is important for HF formation, isoform-specific TAp73- and DeltaNp73-
deficient embryonic and early postnatal mice were examined. In both mutants, the number of CRNs was
reduced, but each of their phenotypes was much milder than in the global p73KO mutant missing both
isoforms. In the TAp73KO mice, the HF of the dorsal HC failed to form, but was present in the ventral HC. In
the DeltaNp73KO mice, the HC had a mild patterning defect along with a shorter HF. Complex interactions
between both isoforms in CRNs may contribute to their crucial activity in the developing brain.