The Journal of Neuroscience, 2002, 22:RC217:1-5
RAPID COMMUNICATION
Citron-Kinase, a Protein Essential to Cytokinesis in Neuronal
Progenitors, Is Deleted in the Flathead Mutant
Rat
Matthew R.
Sarkisian1,
Weiwei
Li1,
Ferdinando
Di Cunto2,
Santosh R.
D'Mello3, and
Joseph J.
LoTurco1
1 Department of Physiology and Neurobiology, University
of Connecticut, Storrs, Connecticut 06269, 2 Department of
Genetics, Biology and Biochemistry, University of Torino, 10126 Torino,
Italy, and 3 Department of Molecular and Cell Biology,
University of Texas at Dallas, Richardson, Texas 75083
Cytokinesis is an essential step in neurogenesis, yet the
mechanisms that control cytokinesis in the developing CNS are not well
understood. The flathead (fh)
mutation in rat results in cytokinesis failure in neural progenitors
followed by apoptosis and a dramatic reduction in CNS growth. Here we
present evidence that the fh mutation is caused by a
single base deletion in exon 1 of the gene encoding
Citron-Kinase (Citron-K). This base deletion causes a premature
stop codon at the 27th codon in the N-terminal kinase domain of
Citron-K, and Western blot and immunocytochemical analysis show that
the Citron-K protein is absent in proliferative zones in
fh/fh mutant embryos. We find that Citron-K protein is normally expressed along the ventricular zone (VZ) surface and localizes to cleavage furrows of both symmetrically and asymmetrically dividing progenitors. In addition, Citron-K colocalizes with RhoA at
cleavage furrows in wild-type (wt) embryos, whereas RhoA
expression is reduced at the VZ surface and is absent from many
cytokinesis furrows in homozygous fh/fh mutants. These
results, together with evidence from a recently described induced
mutation in mice, indicate that the flathead mutation is
in the Citron-K gene and that Citron-K may act with RhoA to ensure the
progression of cytokinesis in neuronal progenitors.
Key words:
Citron; cortical malformation; epilepsy; progenitor; mitosis; neurogenesis; neocortex; Rho
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