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The Journal of Neuroscience, May 15, 2002, 22(10):4036-4044
Cyclin-Dependent Kinase 5/p35 Contributes Synergistically with
Reelin/Dab1 to the Positioning of Facial Branchiomotor and Inferior
Olive Neurons in the Developing Mouse Hindbrain
Toshio
Ohshima1,
Masaharu
Ogawa2,
Kyoko
Takeuchi2,
Satoru
Takahashi3,
Ashok B.
Kulkarni3, and
Katsuhiko
Mikoshiba1
1 Laboratory for Developmental Neurobiology and
2 Cell Culture Development, Brain Science Institute, The
Institute of Physical and Chemical Research (RIKEN), Wako, Saitama
351-0198, Japan, and 3 Functional Genomics Unit, National
Institute of Dental and Craniofacial Research, National Institutes of
Health, Bethesda, Maryland 20892
Cyclin-dependent kinase 5 (Cdk5)/p35 is a serine/threonine kinase,
and its activity is detected primarily in postmitotic neurons. Mice
lacking Cdk5/p35 display migration defects of the cortical neurons in
the cerebrum and cerebellum. In this study, we demonstrate that
although most brainstem nuclei are found in their proper positions, the
motor nucleus of the facial nerve is ectopically located and neurons of
the inferior olive fail to position correctly, resulting in the lack of
their characteristic structures in the hindbrain of Cdk5 / mice.
Despite the defective migration of these neurons, axonal exits of the
facial nerve from brainstem and projections of the inferior cerebellar
axons appear unchanged in Cdk5/ mice. Defective neuronal migration
in Cdk5/ hindbrain was rescued by the neuron-specific expression of
Cdk5 transgene. Because developmental defects of these structures have
been reported in reeler and Dab1 mutant mice, we
analyzed the double-null mutants of p35 and Dab1 and found more
extensive ectopia of VII motor nuclei in these mice. These results
indicate that Cdk5/p35 and Reelin signaling regulates the selective
mode of neuronal migration in the developing mouse hindbrain.
Key words:
Cdk5; p35; reelin; disabled-1; facial branchiomotor
neuron; inferior olive
Copyright © 2002 Society for Neuroscience 0270-6474/02/22104036-09$05.00/0
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