Title

Molecular and cellular regulation of neurogenic cell division: A link between apical cytokinesis and adherens junction complex

Date of Completion

January 2009

Keywords

Biology, Neurobiology

Degree

Ph.D.

Abstract

In embryonic neocortex, neurogenic mitoses are confined to the ventricular zone (VZ) surface and subventricular zone (SVZ). The points of cellular abscission for VZ divisions are immediately adjacent to the adherens junctions at the apical membrane. The mechanisms that couple neurogenic cell abscissions to this apical surface are not known. Citron kinase (CITK), a protein essential to neurogenic cell division, polarizes to the apical membrane in metaphase prior to ingression of the cleavage furrow and becomes confined to midbodies at the VZ surface during cellular abscission. I report that CITK interacts with two proteins, RanGTPase binding protein 9 (RanBPM) and Discs large 5 (Dlg5), which both localize to the adherens junctions. RNAi of RanBPM in vivo decreases the number of midbodies localized to the VZ surface and causes accumulation of cells in M-phase. Dlg5 mutation in mice causes disrupted CITK polarization and decreased M-phase cells at the apical surface of the VZ. Taken together, I conclude that interactions between CITK and RanBPM, and CITK and Dlg5 contribute to progression of events during apical neurogenic cell division. These data provide evidence for a direct molecular and functional link between the midbody and adherens junctional complex. ^