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20
OM&P
Section MOLECULAR NEUROSCIENCE
neurogenesis, while low level allows upper layers generation. We further show that TrkC-T1 controls neocortical cell fate by preventing activation of adapter molecule ShcA, which in turn leads to inhibition of MAP kinase pathway. Manipulating the levels of activity of TrkC-T1, ShcA or Erk has a direct effect on fate determination of cortical progenitors. We further demonstrate that down-regulation of TrkC-T1 levels in late progenitors allows activation of ShcA with consecutive activation of Erk (MAP kinase) and instructs late progenitors to generate upper layer neurons.
Molecular Mechanisms Underlying Area-Specific Circuit Formation in the Mouse Neocortex
Michele Studer*
Institute of Biology Valrose, France. * Presenting e-mail: michele.studer@unice.fr
Despite an apparently similar laminar and cell-type organization, neocortical areas have distinct features in terms of molecular identity, morphology and long-range connectivity of residing projection neurons, leading ultimately to area-specific circuits. Despite its well-defined anatomical character and functional significance, the molecular mechanisms by which neuronal subtypes are specified within cortical layers and across domains as well as their precise assembly into distinct functional neocortical areas, remains largely unknown. Since neocortical areas are first pre-patterned by a set of transcription factors expressed in gradients during development and then acquire a distinct function postnatally (sensory-input versus motor-output), a complex interplay between intrinsic and extrinsic activity-dependent mechanisms might exist during formation of area-specific circuits. This talk will focus on how factors expressed in distinct prospective areas and layers control the ratio and distribution of projection neuron subtypes (intracortical versus subcortical) and how these factors modulate activity-dependent mechanisms in the motor and somatosensory postnatal cortex. Together with epigenetic modifications, we propose that the great variety of projection neurons in the mammalian cerebral cortex is not only due to the existence of genetic programs directing the development of each single neuronal subtype, but also to mechanisms that modify and refine after birth the processes specifying major projection neuron classes. Overall, our data contribute in unraveling some of the developmental mechanisms of how diverse populations of cortical projection neurons are coordinated into high-functional territories and how they interact during assembly of cortical circuits into distinct functional areas.
References
1. Harb K., Magrinelli E., Nicolas C.S, Lukianets N., Frangeul L., Pietri M., Sun T., Sandoz G., Grammont F., Jabaudon D., Studer M.* and Alfano C.* Area-specific development of distinct neocortical neuron subclasses is regulated by postnatal epigenetic modifications. eLife, 2016, Jan 27;5.
2. Alfano C., Magrinelli E., Harb K., Hevner R. F. and Studer M. Postmitotic control of sensory area specification during neocortical development. Nature Communications, 2014 Dec 5;5:5632.
3. Tomassy Srubek G., De Leonibus E., Jabaudon D., Lodato S., Alfano C., Mele A., Macklis J.D. and Studer M. Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI. PNAS, 2010, 107(8): 3576-81.
Behavioral Characterization of SATB 1 (+/-) Heterozygous Mice
I.I. Belousova*, E.A. Epifanova, A.A. Babaev, I.V. Mukhina, V.S. Tarabykin
Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia. * Presenting e-mail: ira.belousova@gmail.com
Satb1 (special AT-rich sequence binding protein 1) gene encodes a matrix protein that regulates chromatin structure and gene expression. In the present study, Satb1 heterozygous (+/-) mice were investigated to unravel the functional role of Satb1 in the brain.
24 Opera Med Physiol 2016 Vol. 2 (S1)
