Comparison of munc-18 and cdk5 expression in the nervous system during mouse embryogenesis.
Cyclin-dependent kinase-5 (Cdk5) and its neuron-specific activator, p35, are essential for the proper migration of neurons. While the defects in p35 null mice are largely confined to the cerebral cortex, the anomalies in cdk5 nullizygous mice are also evident in the hippocampus and cerebellum. This suggested that additional cyclin-like activators, such as Munc-18, must be coexpressed with Cdk5 in some migrating neurons. Therefore, the expression patterns of munc-18 and cdk5 were determined in the developing mouse nervous system by in situ hybridization. In the embryonic day 11.5-13.5 developing neocortex, cdk5 was expressed in the proliferative zone and also in migratory and postmitotic neurons. In contrast, munc-18 messenger RNA was only detected in postmigratory, differentiated neurons. In the cerebellum and the hippocampus, cdk5 was expressed in proliferative, migrating and postmigratory neurons, while munc-18 was expressed in migrating and postmigratory neurons. This supports the hypothesis that Munc-18 could compensate for the loss of p35 in migrating neurons in the hippocampus and cerebellum, but not the cerebral cortex. Munc-18 levels increased substantially during late embryogenesis and into adulthood. Therefore, the function of Munc-18 is most likely relevant to mature neurons and any redundancy with p35 in migration is probably fortuitous.
Han
S H
SH
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Morgan
J I
JI
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D002531:Cerebellum / Q000196:embryology / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D005314:Embryonic and Fetal Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D051938:Munc18 Proteins; D019579:Neocortex / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011247:Pregnancy; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism; D013572:Synaptic Vesicles / Q000502:physiology; D033921:Vesicular Transport Proteins
D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D033921:Vesicular Transport Proteins; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases