Stephanie Bielas, University of Michigan Medical School - USA

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Event date: from 25/01/2019 to 20/12/2019
Seminar canceled due to air transport strikes
Monday, December 9th - h 2:00 p.m.
Seminars Room, NICO
Neuroscience Institute Cavalieri Ottolenghi
Regione Gonzole 10, Orbassano (TO)

Prof. Stephanie Bielas
Associate Professor of Human Genetics
Department of Human Genetics, The University of Michigan Medical School, Ann Arbor, MI, USA

Molecular Dissection of Cell Division Critical for the Developing Brain

Primary microcephaly is a neurodevelopmental disorder characterized by a severe reduction in brain size, generally attributed to a defect in neural progenitor cell proliferation. We recently identified Citron kinase ( CIT ) as a novel genetic basis of primary microcephaly.
CIT is a multidomain protein composed of a N-terminal kinase domain and C-terminal protein interaction domains that allow CIT to be incorporated into the contractile ring during cytokinesis.  We identified pathogenic missense variants that disrupt kinase activity, and truncating variants disrupt both CIT-dependent functions. This genotypic spectrum correlates with clinical severity, with missense variants associated with primary microcephaly with simplified gyral pattern and truncating CIT variants as the basis of micro-lissencephaly. These findings demonstrated that both CIT kinase and structural functions are required for neural progenitor cell cytokinesis, proliferation, and gyri formation.
During brain development, neural progenitor cytokinesis is characterized by baso-apical polarity. We hypothesize that CIT coordinates baso-apical polarized cytokinesis required to maintain neural progenitor multipotency . The molecular components that coordinate this cell biology remain unresolved but are important to understanding brain biology and pathogenesis of developmental disorders. 
Our studies using in vitro human models of neurodevelopment and phosphoproteomics build on human genetics findings to make novel discoveries about normal human brain development and neuropathology of CIT -based microcephaly.

Hosts: Prof. Ferdinando Di Cunto, Dr. Enrica Boda