Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis
We have previously described hypomorphic <i>reelin</i> (<i>Reln</i>) mutant mice, <i>Reln<sup>CTRdel</sup></i>, in which the morphology of the dentate gyrus is distinct from that seen in <i>reeler</i> mice. In the <i>Reln<sup>CT...
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MDPI AG
2020-09-01
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| Series: | Journal of Developmental Biology |
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| Online Access: | https://www.mdpi.com/2221-3759/8/3/20 |
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| author | Seungshin Ha Prem P. Tripathi Ray A. Daza Robert F. Hevner David R. Beier |
| author_facet | Seungshin Ha Prem P. Tripathi Ray A. Daza Robert F. Hevner David R. Beier |
| author_sort | Seungshin Ha |
| collection | DOAJ |
| description | We have previously described hypomorphic <i>reelin</i> (<i>Reln</i>) mutant mice, <i>Reln<sup>CTRdel</sup></i>, in which the morphology of the dentate gyrus is distinct from that seen in <i>reeler</i> mice. In the <i>Reln<sup>CTRdel</sup></i> mutant, the infrapyramidal blade of the dentate gyrus fails to extend, while the suprapyramidal blade forms with a relatively compact granule neuron layer. Underlying this defect, we now report several developmental anomalies in the <i>Reln<sup>CTRdel</sup></i> dentate gyrus. Most strikingly, the distribution of Cajal-Retzius cells was aberrant; Cajal-Retzius neurons were increased in the suprapyramidal blade, but were greatly reduced along the subpial surface of the prospective infrapyramidal blade. We also observed multiple abnormalities of the fimbriodentate junction. Firstly, progenitor cells were distributed abnormally; the “neurogenic cluster” at the fimbriodentate junction was absent, lacking the normal accumulation of Tbr2-positive intermediate progenitors. However, the number of dividing cells in the dentate gyrus was not generally decreased. Secondly, a defect of secondary glial scaffold formation, limited to the infrapyramidal blade, was observed. The densely radiating glial fibers characteristic of the normal fimbriodentate junction were absent in mutants. These fibers might be required for migration of progenitors, which may account for the failure of neurogenic cluster formation. These findings suggest the importance of the secondary scaffold and neurogenic cluster of the fimbriodentate junction in morphogenesis of the mammalian dentate gyrus. Our study provides direct genetic evidence showing that normal RELN function is required for Cajal-Retzius cell positioning in the dentate gyrus, and for formation of the fimbriodentate junction to promote infrapyramidal blade extension. |
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| series | Journal of Developmental Biology |
| spelling | doaj.art-8e1bcba0117a41f594838f92a9ddffe02023-11-20T14:14:33ZengMDPI AGJournal of Developmental Biology2221-37592020-09-01832010.3390/jdb8030020Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade MorphogenesisSeungshin Ha0Prem P. Tripathi1Ray A. Daza2Robert F. Hevner3David R. Beier4Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA 98101, USACenter for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USACenter for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USACenter for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USACenter for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA 98101, USAWe have previously described hypomorphic <i>reelin</i> (<i>Reln</i>) mutant mice, <i>Reln<sup>CTRdel</sup></i>, in which the morphology of the dentate gyrus is distinct from that seen in <i>reeler</i> mice. In the <i>Reln<sup>CTRdel</sup></i> mutant, the infrapyramidal blade of the dentate gyrus fails to extend, while the suprapyramidal blade forms with a relatively compact granule neuron layer. Underlying this defect, we now report several developmental anomalies in the <i>Reln<sup>CTRdel</sup></i> dentate gyrus. Most strikingly, the distribution of Cajal-Retzius cells was aberrant; Cajal-Retzius neurons were increased in the suprapyramidal blade, but were greatly reduced along the subpial surface of the prospective infrapyramidal blade. We also observed multiple abnormalities of the fimbriodentate junction. Firstly, progenitor cells were distributed abnormally; the “neurogenic cluster” at the fimbriodentate junction was absent, lacking the normal accumulation of Tbr2-positive intermediate progenitors. However, the number of dividing cells in the dentate gyrus was not generally decreased. Secondly, a defect of secondary glial scaffold formation, limited to the infrapyramidal blade, was observed. The densely radiating glial fibers characteristic of the normal fimbriodentate junction were absent in mutants. These fibers might be required for migration of progenitors, which may account for the failure of neurogenic cluster formation. These findings suggest the importance of the secondary scaffold and neurogenic cluster of the fimbriodentate junction in morphogenesis of the mammalian dentate gyrus. Our study provides direct genetic evidence showing that normal RELN function is required for Cajal-Retzius cell positioning in the dentate gyrus, and for formation of the fimbriodentate junction to promote infrapyramidal blade extension.https://www.mdpi.com/2221-3759/8/3/20reelin proteinhippocampusdentate gyruspostnatal developmentmigrationneurogenesis |
| spellingShingle | Seungshin Ha Prem P. Tripathi Ray A. Daza Robert F. Hevner David R. Beier Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis Journal of Developmental Biology reelin protein hippocampus dentate gyrus postnatal development migration neurogenesis |
| title | Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis |
| title_full | Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis |
| title_fullStr | Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis |
| title_full_unstemmed | Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis |
| title_short | Reelin Mediates Hippocampal Cajal-Retzius Cell Positioning and Infrapyramidal Blade Morphogenesis |
| title_sort | reelin mediates hippocampal cajal retzius cell positioning and infrapyramidal blade morphogenesis |
| topic | reelin protein hippocampus dentate gyrus postnatal development migration neurogenesis |
| url | https://www.mdpi.com/2221-3759/8/3/20 |
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