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.
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.
Ohshima
Toshio
T
Laboratory for Developmental Neurobiology, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198, Japan. ohshima@brain.riken.go.jp
Ogawa
Masaharu
M
Takeuchi
Kyoko
K
Takahashi
Satoru
S
Kulkarni
Ashok B
AB
Mikoshiba
Katsuhiko
K
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002465:Cell Movement; D002828:Choristoma / Q000209:etiology / Q000473:pathology*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000172:deficiency / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005145:Face / Q000294:innervation; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D009474:Neurons / Q000473:pathology; D009847:Olivary Nucleus / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D000091042:Reelin Protein; D012249:Rhombencephalon / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D012697:Serine Endopeptidases; D015398:Signal Transduction; D019076:Transgenes
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases