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Cajal-Retzius neurons are required for the development of the human hippocampal fissure.

  • Meyer, Gundela1
  • González-Arnay, Emilio2
  • Moll, Ute3
  • Nemajerova, Alice3
  • Tissir, Fadel4
  • González-Gómez, Miriam1
  • 1 Department of Basic Medical Sciences, University La Laguna, La Laguna, Spain. , (Spain)
  • 2 Department of Anatomy and Neuroscience, Autonomous University Madrid, Madrid, Spain. , (Spain)
  • 3 Department of Pathology, Stony Brook University, Stony Brook, NY, USA.
  • 4 Developmental Neurobiology Group, Institute of NeuroScience, UCL Louvain, Brussels, Belgium. , (Belgium)
Published Article
Journal of anatomy
Publication Date
Sep 01, 2019
DOI: 10.1111/joa.12947
PMID: 30861578


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 later-appearing 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. © 2019 Anatomical Society.

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