![]() ![]() Moreover, our data strongly indicates that Reelin from Cajal-Retzius cells is important for the typical inside-out laminar cortical development but seems to be dispensable for pre-plate splitting. Thus, to unravel the function of Reelin at different developmental stages (from embryonic to adult) as well as to gain insight in the potential distinct contribution of Reelin from different cell-types, we have generated three Reelin deficient conditional transgenic lines which allow us to ubiquitously delete Reelin in a temporally-controlled manner (Cre fR/fR) or selectively remove Reelin from Cajal-Retzius cells (CR fR/fR) or GABAergic interneurons (Gad fR/fR).Īnalysis of the cortical organization using layer-specific markers reveals that, unlike the reeler mouse, none of our transgenic lines shows the characteristic inversion of cortical layers. However the study of the effects of Reelin signaling in the adult brain is difficult in the reeler mouse model due to the failed migration and mispositioning during development. The reeler mouse presents several morphological defects including a failed pre-plate splitting that causes a roughly inverted neuronal layering in the cortex, mispositioning of pyramidal neurons as well as granular cells on the dentate gyrus and profound cerebellar hypoplasia. In this context, one of the most studied models has been the reeler mouse which presents a characteristic phenotype caused by an autosomal mutation in the Rln gene. The malpositioning of cortical neurons is a result of abnormal migration and could cause severe layering malformations with functional consequences related with neurodevelopmental diseases such as Schizophrenia, Autism and Epilepsy. In the neocortex, postmitotic neurons migrate in an ordered sequence that determines the normal “inside-out” layer formation. At the embryonic stage, Reelin is expressed mainly by Cajal-Retzius cells on the developing brain whereas at perinatal stages its expression gradually disappears from Cajal-Retzius cells and starts to be expressed by GABAergic interneurons of the cortex and hippocampus. Reelin acts through the binding to its canonical receptors (apolipoprotein E receptor 2, ApoER2 and very low density lipoprotein receptor, VLDLR) which trigger a complex signaling cascade involving numerous kinases and the adaptor protein Dab1. ![]() ![]() Reelin is a large extracellular matrix glycoprotein with a crucial role both during brain development, where it is key for neuronal migration and for the formation of the layered structure of cerebral cortex and cerebellum, and in the adulthood, where it is involved in adult synaptic plasticity, including neurogenesis in the dentate gyrus and dendritogenesis amongst other processes. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |