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[P1.02]: Staufen 2 regulates neural fate determination and neuronal migration during mammalian cortical development
Author(s) -
Vessey J.P.,
Burns S.E.,
Kaplan D.R.,
Miller F.D.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.043
Subject(s) - miller , sick child , general hospital , medicine , psychology , pediatrics , biology , ecology
The mammalian neocortex is organised into six layers, each defined by the densities, morphologies and the intrinsic and extrinsic connections of its constituent cells. The laminar identity of an individual cortical neuron depends on the time of its “birth”. Neurons destined for the infragranular layers are born at early stages, while supragranular neurons are born at later stages of embryonic development, resulting in an “inside-out” formation of the cortex. Various key molecules have already been identified and described that orchestrate developmental processes like neurogenesis, cell cycle exit, neuronal differentiation and migration, including proneural genes, transcription factors and guidance molecules. Members of the Eph/Ephrin-system are also expressed in the developing cortex. Many previous studies have shown that ephrins and their receptors can act as repulsive or attractive cues for growing axons and migrating neurons. Moreover, our recent in vitro study suggested that ephrin-A5 can also regulate the adhesive properties of cortical neurons, suggesting a possible role during cortical layer formation (Zimmer et al., 2007. J. Neurosci. 27, 5642). Therefore, we analyzed the layering of the somatosensory cortex in ephrin–A5 deficient mice. Although the thickness of the cortex remains unchanged, the relative sizes of the infraand supragranular layers are altered in ephrin–A5 deficient animals. While the layers 2/3 and 4 are thinner, the thickness of layers 5 and 6 is increased in the knockout mice. The layer-specific expression patterns of EphA5, EphA8 and EphB6 are shifted according to the expansion of the deeper layers. Consistently, the number of cells positive for the transcription factors Otx–1 and 2, which are expressed by a subset of layer 5 and 6 neurons, is increased in the ephrin-A5 deficient mice. These data indicate that ephrin–A5 is involved in the regulation of the relative proportion of supraand infragranular layers in the developing cortex.