Callosal axon guidance defects in p35?/? mice

Kwon, Young T.; Tsai, Li‐Huei; Crandall, James E.

doi:10.1002/(sici)1096-9861(19991213)415:2<218::aid-cne6>3.0.co;2-f

Cited by 67 publications

(46 citation statements)

References 63 publications

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“…The possibility that loss of p35 function could result, directly, in aberrant synaptic contacts is attractive, given that p35 is thought to play a critical role in axon formation and guidance, and that the p35 mRNA signal is present in axonal bundles and is associated with growth cone actin cytoskeleton (Paglini and Caceres, 2001). Furthermore, although in most brain regions p35 is expressed at high levels only during early stages of development (associated with migration of neurons to their final destination and their differentiation), it remains at high levels of expression in the pyriform cortex and in the pyramidal layers of the hippocampus, where its presence in axonal bundles may influence neuronal plasticity in the adult (Kwon et al, 1999;Paglini and Caceres, 2001).…”

Section: Structural and Functional Evidence Of Recurrent Excitationmentioning

confidence: 99%

“…In contrast, whereas the p35 knock-out mouse also demonstrates cortical lamination defects, it suffers from only sporadic adult lethality and exhibits spontaneous limbic-like seizures (Tsai et al, 1994;Ohshima et al, 1996;Gilmore et al, 1998;Tanaka et al, 2001;Wenzel et al, 2001;Gupta et al, 2003). Many brain regions of p35Ϫ/Ϫ animals exhibit structural abnormalities (Chae et al, 1997;Kwon and Tsai, 1998;Kwon et al, 1999). Our studies have focused on specific disorganizational patterns observed in the hippocampal dentate gyrus (Wenzel et al, 2001).…”

Section: Introductionmentioning

confidence: 97%

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Physiological and Morphological Characterization of Dentate Granule Cells in the p35 Knock-Out Mouse Hippocampus: Evidence for an Epileptic Circuit

Patel¹,

Wenzel²,

Schwartzkroin³

2004

J. Neurosci.

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There is a high correlation between pediatric epilepsies and neuronal migration disorders. What remains unclear is whether there are intrinsic features of the individual dysplastic cells that give rise to heightened seizure susceptibility, or whether these dysplastic cells contribute to seizure activity by establishing abnormal circuits that alter the balance of inhibition and excitation. Mice lacking a functional p35 gene provide an ideal model in which to address these questions, because these knock-out animals not only exhibit aberrant neuronal migration but also demonstrate spontaneous seizures.Extracellular field recordings from hippocampal slices, characterizing the input-output relationship in the dentate, revealed little difference between wild-type and knock-out mice under both normal and elevated extracellular potassium conditions. However, in the presence of the GABA A antagonist bicuculline, p35 knock-out slices, but not wild-type slices, exhibited prolonged depolarizations in response to stimulation of the perforant path. There were no significant differences in the intrinsic properties of dentate granule cells (i.e., input resistance, time constant, action potential generation) from wild-type versus knock-out mice. However, antidromic activation (mossy fiber stimulation) evoked an excitatory synaptic response in over 65% of granule cells from p35 knock-out slices that was never observed in wild-type slices. Ultrastructural analyses identified morphological substrates for this aberrant excitation: recurrent axon collaterals, abnormal basal dendrites, and mossy fiber terminals forming synapses onto the spines of neighboring granule cells. These studies suggest that granule cells in p35 knock-out mice contribute to seizure activity by forming an abnormal excitatory feedback circuit.

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Section: Structural and Functional Evidence Of Recurrent Excitationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Physiological and Morphological Characterization of Dentate Granule Cells in the p35 Knock-Out Mouse Hippocampus: Evidence for an Epileptic Circuit

Patel¹,

Wenzel²,

Schwartzkroin³

2004

J. Neurosci.

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“…Unlike other CDKs, CDK5 has the highest expression level and kinase activity in neurons and has crucial functions in a wide range of cellular events, including protein trafficking, cell death, neurite and synapse development, dopamine response, learning, and memory. Defects in axon guidance were observed in p35 knock-out mice (Kwon et al, 1999) and in Drosophila with abnormal CDK5 activity (Connell-Crowley et al, 2000). In cultured cortical neurons, suppression of CDK5 activity inhibited neurite outgrowth, whereas the introduction of exogenous p35 and CDK5 led to the elaboration of longer neurites (Nikolic et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Neuronal Morphogenesis Is Regulated by the Interplay between Cyclin-Dependent Kinase 5 and the Ubiquitin Ligase Mind Bomb 1

Choe

Liao²,

Zhang³

et al. 2007

J. Neurosci.

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“…Cdk5 Ϫ/Ϫ mice exhibit widespread disruption of normal lamination in brain regions (2), and similar cortical lamination disruption has also been reported in the p35 Ϫ/Ϫ mice (3). Furthermore, the defects observed in the fasciculation of axon tracts in p35 Ϫ/Ϫ mice suggest that Cdk5 is also involved in axon patterning (4).…”

mentioning

confidence: 99%

Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Cyclin-dependent kinase (Cdk)5 is a key regulator of neural development. We have previously demonstrated that Cdk5͞p35 are localized to the postsynaptic muscle and are implicated in the regulation of neuregulin͞ErbB signaling in myotube culture. To further elucidate whether Cdk5 activity contributes to neuromuscular junction (NMJ) development in vivo, the NMJ of Cdk5 ؊/؊ mice was examined. Consistent with our previous demonstration that Cdk5 phosphorylates ErbB2͞3 to regulate its tyrosine phosphorylation, we report here that the phosphorylation of ErbB2 and ErbB3 and the ErbB2 kinase activity are reduced in Cdk5-deficient muscle. In addition, Cdk5 ؊/؊ mice also display morphological abnormalities at the NMJ pre-and postsynaptically. Whereas the outgrowth of the main nerve trunk is grossly normal, the intramuscular nerve projections exhibit profuse and anomalous branching patterns in the Cdk5 ؊/؊ embryos. The central band of acetylcholine receptor (AChR) clusters is also wider in Cdk5 ؊/؊ diaphragms, together with the absence of S100 immunoreactivity along the phrenic nerve during late embryonic stages. Moreover, we unexpectedly discovered that the agrin-induced formation of large AChR clusters is significantly increased in primary muscle cultures prepared from Cdk5-null mice and in C2C12 myotubes when Cdk5 activity was suppressed. These abnormalities are accompanied by elevated frequency of miniature endplate potentials in Cdk5-null diaphragm. Taken together, our findings reveal the essential role of Cdk5 in regulating the development of motor axons and neuromuscular synapses in vivo.agrin ͉ Cdk5 ͉ ErbB receptor ͉ neuromuscular junction

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Callosal axon guidance defects in p35?/? mice

Cited by 67 publications

References 63 publications

Physiological and Morphological Characterization of Dentate Granule Cells in the p35 Knock-Out Mouse Hippocampus: Evidence for an Epileptic Circuit

Physiological and Morphological Characterization of Dentate Granule Cells in the p35 Knock-Out Mouse Hippocampus: Evidence for an Epileptic Circuit

Neuronal Morphogenesis Is Regulated by the Interplay between Cyclin-Dependent Kinase 5 and the Ubiquitin Ligase Mind Bomb 1

Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice

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