INVESTIGATING THE ROLE OF microRNAS DURING MAMMALIAN BRAIN DEVELOPMENT

GONZALEZ, PAULA; AGUIRRE, PAULA A.; SOMMER, CHRIS; FEDEDA, JUAN PABLO

Chascomús

Taller; IV Taller de Biología Celular y del Desarrollo; 2018

Laboratorio de Biología del Desarrollo IIB-INTECh

The emergence of the cerebral cortex during evolu=on allowed the brain to enhance the sensing, interpretationandresponsetothesurroundingworldstimulithroughaconsciousstate.Recently,ithasbeen shown that microRNAs are essential for mammalian cortex development. However, thecontribution of individual microRNAs in the regulation of brain differentiation mechanisms remainsbastlyunknown.Wedevelopedinvitroscreeningmethodologiescoupled toinvivostudiesinorder toinvestigate theroleofmicroRNAsindifferentprocessesrelatedtocorticogenesis,includingregulationofcelldivision,migrationandmicroRNAactivity.Usingahigh-contentscreenandmousegene=cs,weidentifiedmiR34/449 family as a key regulator of radial glial cell differen=a=on in the developing cerebral cortex.Analyzing miR-34/449 knockout (KO) mouse embryos, we found significant spindle misorientation phenotypes in cortical progenitors, resulting in an excess of radial glia cells at the expense ofneurogenicintermediateprogenitors,showingthatmiR-34/449isrequiredforthe=melygenerationofcorticalneurons.Usingasimilarstrategy,wescreenedthroughallcorticallyexpressedmicroRNAsand found that autistic syndrome associated miR-107 promotes cell migra=on in vitro. Finally, using amicroRNAac=vitysensor,wescreenedthehumankinomeandfoundthatseveralessentialkinasesforcorticallaminationarenecessaryformicroRNAactivity.Bycouplinginvitroandinvivoassays,ourdata indicate that microRNAs and their regulators could be implicated in key cellular processes during corticaldevelopment