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Séminaire impromptu - Karine LoulierProbing at neural diversity and brain cytoarchitecture using multicolor strategies

Abstract :

 The mammalian cerebral cortex relies on many distinct cell types to exert its high cognitive functions.
How neural diversity arises from a seemingly homogeneous population of cortical progenitors and how individual progenitors and their descent cooperate to establish complex brain architecture remain challenging questions not fully addressed in vivo. We have elaborated several multicolor strategies based on updated versions of Brainbow constructs that provide an expanded palette of color markers (blue, cyan, yellow and red fluorescent proteins) addressed to specific subcellular compartments (Magic Markers; Loulier et al, 2014). In utero electroporation of cortical progenitors with integrative Magic Markers constructs enables us to resolve and track multiple clones of protoplasmic astrocytes, thus providing valuable information on glial network maturation over time.
We have also generated transgenic mouse lines expressing Magic Markers constructs under the broadly active CAG promoter. Intercrossed with tamoxifen-inducible or constitutive Cre mice, Magic Markers mice display widespread expression of fluorescent markers in various embryonic and adult tissues (including neural, epithelial and muscle tissues) and multiple distinct cell types. Delivery of Cre-expressing plasmid in Magic Markers mouse cortical progenitors yields robust multicolor labeling of both early- (progenitors) and late-born neural cells (neurons, astrocytes, oligodendrocytes) from embryonic to adult stages. Following early and sparse recombination in the dorsal telencephalon, heterogeneous columns of clonally related cells displaying distinct combinations of color labels are obtained.
Upon dense recombination, multicolor cell labeling allows one to individualize cells of distinct types and to analyze their anatomical relationships. Finally, Magic Markers strategies constitute invaluable assets to understand how neuronal and glial cells born from nearby cortical progenitors cooperate to build an operative brain, while offering a new way to decipher neural diversity among and across distinct lineages.

Selected publications

Loulier K, Barry R, Mahou P, Le Franc Y, Supatto W, Matho KS, Ieng S, Fouquet S, Dupin E, Benosman R, Chédotal A, Beaurepaire E, Morin X, Livet J. Multiplex lineage tracking with combinatorial labels. Neuron 2014, 81:505-20

Mahou P., Zimmerley M.*, Loulier K.*, Matho K.S., Labroille G., Morin X., Supatto W., Livet J., Débarre D., Beaurepaire E. Multicolor two-photon tissue imaging by wavelength mixing. Nat Methods 2012, 9(8):815-8. * Equal contribution.

Loulier K.*, Lathia J.*, Marthiens V., Relucio J., Mughal M.R., Tang S., Coksaygan T., Hall P.E., Chigurupati S., Patton B., Colognato H., Rao M.S., Mattson M.P., Haydar T.F.†, ffrench-Constant C. †. β1 integrin maintains integrity of the embryonic neocortical stem cell niche – PLoS Biology 2009, 8:e1000176 *,† Equal contribution.