Specific inhibition of cyclin-dependent kinase 5 activity induces motor neuron development in vivo.
Cyclin-dependent kinase 5 (cdk5) is a ubiquitous protein activated by specific activators, p35 and p39. Cdk5 regulates neuronal migration, differentiation, axonogenesis, synaptic transmission and apoptosis. However, its role in motor neuron development remains unexplored. Here, using gain and loss-of-function analyses in developing zebrafish embryos, we report that cdk5 plays a critical role in spinal and cranial motor neuron development. Cdk5 knockdown results in supernumerary spinal and cranial motor neurons. While a dominant negative, kinase-dead cdk5 promotes the generation of supernumerary motor neurons; over-expression of cdk5 suppresses motor neuron development. Thus, modulating cdk5 activity seems promising in inducing motor neuron development in vivo.
Kanungo
Jyotshnabala
J
Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4130, USA. kanungoj@mail.nih.gov
Zheng
Ya-Li
YL
Amin
Niranjana D
ND
Kaur
Sukhbir
S
Ramchandran
Ramani
R
Pant
Harish C
HC
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000502:physiology; D055785:Gene Knockdown Techniques; D009046:Motor Neurons / Q000201:enzymology / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
D016376:Oligonucleotides, Antisense; D051360:Cyclin-Dependent Kinase 5