Publication Date:
2009-09-18
Description:
The cerebral cortex is a laminated sheet of neurons composed of the arrays of intersecting radial columns. During development, excitatory projection neurons originating from the proliferative units at the ventricular surface of the embryonic cerebral vesicles migrate along elongated radial glial fibres to form a cellular infrastructure of radial (vertical) ontogenetic columns in the overlaying cortical plate. However, a subpopulation of these clonally related neurons also undergoes a short lateral shift and transfers from their parental to the neighbouring radial glial fibres, and intermixes with neurons originating from neighbouring proliferative units. This columnar organization acts as the primary information processing unit in the cortex. The molecular mechanisms, role and significance of this lateral dispersion for cortical development are not understood. Here we show that an Eph receptor A (EphA) and ephrin A (Efna) signalling-dependent shift in the allocation of clonally related neurons is essential for the proper assembly of cortical columns. In contrast to the relatively uniform labelling of the developing cortical plate by various molecular markers and retrograde tracers in wild-type mice, we found alternating labelling of columnar compartments in Efna knockout mice that are caused by impaired lateral dispersion of migrating neurons rather than by altered cell production or death. Furthermore, in utero electroporation showed that lateral dispersion depends on the expression levels of EphAs and ephrin-As during neuronal migration. This so far unrecognized mechanism for lateral neuronal dispersion seems to be essential for the proper intermixing of neuronal types in the cortical columns, which, when disrupted, might contribute to neuropsychiatric disorders associated with abnormal columnar organization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874978/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874978/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Torii, Masaaki -- Hashimoto-Torii, Kazue -- Levitt, Pat -- Rakic, Pasko -- R01 DA022785/DA/NIDA NIH HHS/ -- R01 DA022785-03/DA/NIDA NIH HHS/ -- R01 DA023999/DA/NIDA NIH HHS/ -- R01 DA023999-01A1/DA/NIDA NIH HHS/ -- R01 DA023999-02/DA/NIDA NIH HHS/ -- R01 NS014841/NS/NINDS NIH HHS/ -- R01 NS014841-30/NS/NINDS NIH HHS/ -- R01 NS014841-31/NS/NINDS NIH HHS/ -- R01 NS038296/NS/NINDS NIH HHS/ -- R01 NS038296-09/NS/NINDS NIH HHS/ -- R01 NS038296-10/NS/NINDS NIH HHS/ -- England -- Nature. 2009 Sep 24;461(7263):524-8. doi: 10.1038/nature08362. Epub 2009 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA. masaaki.torii@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759535" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Cell Movement
;
Cerebral Cortex/anatomy & histology/cytology/*embryology/metabolism
;
Ephrins/deficiency/genetics/*metabolism
;
Mice
;
Mice, Knockout
;
Neocortex/cytology/metabolism
;
Neurons/*cytology/*metabolism
;
Organogenesis
;
Rats
;
Receptors, Eph Family/deficiency/genetics/*metabolism
;
*Signal Transduction
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
