Mouse Brain Development pp 241-253

Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 30)

The Role of the p35/cdk5 Kinase in Cortical Development

  • Young T. Kwon
  • Li-Huei Tsai

Abstract

Extensive studies on the mouse mutant reeler have revealed many of the fundamental characteristics of neocortical development (Caviness and Rakic 1978; Caviness 1982; Caviness et al. 1988). The finding of another spontaneously occurring mouse mutant, scrambler which exhibits nearly identical phenotypes with reeler suggests that the gene products mutated in the strains, mdab-1 and reelin, respectively, act in a common signaling pathway during cortical development (Sweet et al. 1996; Gonzalez et al. 1997; Howell et al. 1997; Sheldon et al. 1997; Ware et al. 1997; Rice et al. 1998). However, the vast complexity of events that must occur to set up the architecture of the cerebral cortex leads to the idea that multiple proteins are essential during cortical development. The p35/cdk5 kinase complex is one such molecular entity. Mouse knockouts of both p35 and cdk5 lead to disruptions of cortical lamination (Ohshima et al. 1996; Chae et al. 1997). Interestingly, the phenotype of the embryonic cerebral wall and adult neocortex in these mice is suggestive of but distinct from that of reeler or scrambler implying that a different essential function during cortical development may be disrupted in mice lacking p35 or cdk5 (Gilmore et al. 1998; Kwon and Tsai 1998).

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References

  1. Allen KM, Gleeson JG, Bagrodia S, Partington MW, MacMillan JC, Cerione RA, Mulley JC, Walsh CA (1998) PAK3 mutation in nonsyndromic X-linked mental retardation. Nat Genet 20: 25–30PubMedCrossRefGoogle Scholar
  2. Beaudette KN, Lew J, Wang JH (1993) Substrate specificity characterization of a cdc2-like protein kinase purified from bovine brain. J Biol Chem 268: 20 825–20 830Google Scholar
  3. Billuart P, Bienvenu T, Ronce N, des Portes V, Vinet MC, Zemni R, Crollius HR, Carrie A, Fauchereau F, Cherry M, Briault S, Hamel B, Fryns JP, Beldjord C, Kahn A, Moraine C, Chelly J (1998) Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. Nature 392: 923–926PubMedCrossRefGoogle Scholar
  4. Brown NR, Noble ME, Endicott JA, Garman EF, Wakatsuki S, Mitchell E, Rasmussen B, Hunt T, Johnson LN (1995) The crystal structure of cyclin A. Structure 3: 1235–1247PubMedCrossRefGoogle Scholar
  5. Cai XH, Tomizawa K, Tang D, Lu YF, Moriwaki A, Tokuda M, Nagahata S, Hatase O, Matsui H (1997) Changes in the expression of novel Cdk5 activator messenger RNA (p39nck5ai mRNA) during rat brain development. Neurosci Res 28: 355–360PubMedCrossRefGoogle Scholar
  6. Caviness VSJ (1982) Neocortical histogenesis in normal and reeler mice: a developmental study based upon [3H]thymidine autoradiography. Dev Brain Res 4: 293–302CrossRefGoogle Scholar
  7. Caviness VSJ, Rakic P (1978) Mechanisms of cortical development: a view from mutations in mice. Annu Rev Neurosci 1: 297–326PubMedCrossRefGoogle Scholar
  8. Caviness VSJ, Crandall JE, Edwards MA (1988) The reeler malformation: implications for neocortical histogenesis. In: Peters A, Jones EG (eds) Cerebral cortex, vol 7. Plenum Press, New York, pp 59–89CrossRefGoogle Scholar
  9. Chae T, Kwon YT, Bronson R, Dikkes P, Li E, Tsai LH (1997) Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 18: 29–42PubMedCrossRefGoogle Scholar
  10. D’Adamo P, Menegon A, Lo Nigro C, Grasso M, Gulisano M, Tamanini F, Bienvenu T, Gedeon AK, Oostra B, Wu SK, Tandon A, Valtorta F, Balch WE, Chelly J, Toniolo D (1998) Mutations in GDI1 are responsible for X-linked non-specific mental retardation. Nat Genet 19: 134–139PubMedCrossRefGoogle Scholar
  11. Delalle I, Bhide PG, Caviness VS Jr, Tsai LH (1997) Temporal and spatial patterns of expression of p35, a regulatory subunit of cyclin-dependent kinase 5, in the nervous system of the mouse. J Neurocytol 26: 283–296PubMedCrossRefGoogle Scholar
  12. des Portes V, Pinard JM, Billuart P, Vinet MC, Koulakoff A, Carrie A, Gelot A, Dupuis E, Motte J, Berwald-Netter Y, Catala M, Kahn A, Beldjord C, Chelly J (1998) A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell 92: 51–61PubMedCrossRefGoogle Scholar
  13. Gilmore EC, Ohshima T, Goffinet AM, Kulkarni AB, Herrup K (1998) Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex. J Neurosci 18: 6370–6377PubMedGoogle Scholar
  14. Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA (1998) Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92: 63–72PubMedCrossRefGoogle Scholar
  15. Gonzalez JL, Russo CJ, Goldowitz D, Sweet HO, Davisson MT, Walsh CA (1997) Birthdate and cell marker analysis of scrambler: a novel mutation affecting cortical development with a reeler-like phenotype. J Neurosci 17: 9204–9211PubMedGoogle Scholar
  16. Howell BW, Hawkes R, Soriano P, Cooper JA (1997) Neuronal position in the developing brain is regulated by mouse disabled-1. Nature 389: 733–737PubMedCrossRefGoogle Scholar
  17. Huang QQ, Lee KY, Wang JH (1996) A novel yeast protein showing specific association with the cyclin-dependent kinase 5. FEBS Lett 378: 48–50PubMedCrossRefGoogle Scholar
  18. Ino H, Ishizuka T, Chiba T, Tatibana M (1994) Expression of CDK5 (PSSALRE kinase), a neural cdc2-related protein kinase, in the mature and developing mouse central and peripheral nervous systems. Brain Res 661: 196–206PubMedCrossRefGoogle Scholar
  19. Ishiguro K, Kobayashi S, Omori A, Takamatsu M, Yonekura S, Anzai K, Imahori K, Uchida T (1994) Identification of the 23 kDa subunit of tau protein kinase II as a putative activator of cdk5 in bovine brain. FEBS Lett 342: 203–208PubMedCrossRefGoogle Scholar
  20. Kobayashi S, Ishiguro K, Omori A, Takamatsu M, Arioka M, Imahori K, Uchida T (1993) A cdc2-related kinase PSSALRE/cdk5 is homologous with the 30 kDa subunit of tau protein kinase II, a proline-directed protein kinase associated with microtubule. FEBS Lett 335: 171–175PubMedCrossRefGoogle Scholar
  21. Kwon YT, Tsai LH (1998) A novel disruption of cortical development in p35-/- mice distinct from reeler. J Comp Neurol 395: 510–522PubMedCrossRefGoogle Scholar
  22. Kwon YT, Tsai LH, Crandall JE (1999) Callosal axon guidance defects in p35-/- mice. J Comp Neurol 415: 218–229PubMedCrossRefGoogle Scholar
  23. Lee KY, Helbing CC, Choi KS, Johnston RN, Wang JH (1997) Neuronal Cdc2-like kinase (Nclk) binds and phosphorylates the retinoblastoma protein. J Biol Chem 272:5622–5626PubMedCrossRefGoogle Scholar
  24. Lew J, Beaudette K, Litwin CM, Wang JH (1992) Purification and characterization of a novel proline-directed protein kinase from bovine brain. J Biol Chem 267: 13 383–13 390Google Scholar
  25. Lew J, Wang JH (1995) Neuronal cdc2-like kinase. Trends Biochem Sci 20: 33–37PubMedCrossRefGoogle Scholar
  26. Lew J, Huang QQ, Qi Z, Winkfein RJ, Aebersold R, Hunt T, Wang JH (1994) A brain-specific activator of cyclin-dependent kinase 5. Nature 371: 423–426PubMedCrossRefGoogle Scholar
  27. Matsubara M, Kusubata M, Ishiguro K, Uchida T, Titani K, Taniguchi H (1996) Site-specific phosphorylation of synapsin I by mitogen-activated protein kinase and Cdk5 and its effects on physiological functions. J Biol Chem 271:21 108–21 113Google Scholar
  28. Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, Harlow E, Tsai LH (1992) A family of human cdc2-related protein kinases. EMBO J 11: 2909–2917PubMedGoogle Scholar
  29. Nikolic M, Dudek H, Kwon YT, Ramos YF, Tsai LH (1996) The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev 10: 816–825PubMedCrossRefGoogle Scholar
  30. Nikolic M, Chou MM, Lu W, Mayer BJ, Tsai LH (1998) The p35/cdk5 kinase is a neuron-specific Rac effector that inhibits Pakl activity. Nature 395: 194–198PubMedCrossRefGoogle Scholar
  31. Ohshima T, Ward JM, Huh CG, Longenecker G, Veeranna, Pant HC, Brady RO, Martin LJ, Kulkarni AB (1996) Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci USA 93:11 173–11 178Google Scholar
  32. Paglini G, Pigino G, Kunda P, Morfini G, Maccioni R, Quiroga S, Ferreira A, Caceres A (1998) Evidence for the participation of the neuron-specific CDK5 activator P35 during lamininenhanced axonal growth. J Neurosci 18: 9858–9869PubMedGoogle Scholar
  33. Patrick GN, Zhou P, Kwon YT, Howley PM, Tsai LH (1998) p35, the neuronal-specific activator of cyclin-dependent kinase 5 (Cdk5) is degraded by the ubiquitin-proteasome pathway. J Biol Chem 273:24 057–24 064Google Scholar
  34. Patrick GN, Zukerberg L, Nikolic M, Monte SDL, Dikkes P, Tsai LH (1999) Conversion of p35 to p25 deregulates cdk5 activity and promotes neurodegeneration. Nature 402: 615–622PubMedCrossRefGoogle Scholar
  35. Philpott A, Porro EB, Kirschner MW, Tsai LH (1997) The role of cyclin-dependent kinase 5 and a novel regulatory subunit in regulating muscle differentiation and patterning. Genes Dev 11: 1409–1421PubMedCrossRefGoogle Scholar
  36. Philpott A, Tsai LH, Kirschner MW (1999) Neuronal differentiation and patterning in Xenopus: the role of cdk5 and a novel activator xp35.2. Dev Biol 20: 119–132CrossRefGoogle Scholar
  37. Pigino G, Paglini G, Ulloa L, Avila J, Caceres A (1997) Analysis of the expression, distribution and function of cyclin dependent kinase 5 (cdk5) in developing cerebellar macroneurons. J Cell Sci 110: 257–270PubMedGoogle Scholar
  38. Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F, Dobyns WB, Caskey CT, Ledbetter DH (1993) Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats. Nature 364: 717–721PubMedCrossRefGoogle Scholar
  39. Rice DS, Sheldon M, D’Arcangelo G, Nakajima K, Goldowitz D, Curran T (1998) Disabled-1 acts downstream of reelin in a signaling pathway that controls laminar organization in the mammalian brain. Development 125: 3719–3729PubMedGoogle Scholar
  40. Sapir T, Elbaum M, Reiner 0 (1997) Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit. EMBO J 16: 6977–6984Google Scholar
  41. Sheldon M, Rice DS, D’Arcangelo G, Yoneshima H, Nakajima K, Mikoshiba K, Howell BW, Cooper JA, Goldowitz D, Curran T (1997) Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice. Nature 389: 730–733PubMedCrossRefGoogle Scholar
  42. Shuang R, Zhang L, Fletcher A, Groblewski GE, Pevsner J, Stuenkel EL (1998) Regulation of Munc-18/syntaxin lA interaction by cyclin-dependent kinase 5 in nerve endings. J Biol Chem 273: 4957–4966PubMedCrossRefGoogle Scholar
  43. Songyang Z, Lu KP, Kwon YT, Tsai LH, Filhol O, Cochet C, Brickey DA, Soderling TR, Bartleson C, Graves DJ, DeMaggio AJ, Hoekstra MF, Blenis J, Hunter T, Cantley LC (1996) A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erkl. Mol Cell Biol 16: 6486–6493PubMedGoogle Scholar
  44. Strobel G (1997) Disordering the brain gives clues to brain disorders. Focus 1: 1, 6Google Scholar
  45. Sweet HO, Bronson RT, Johnson KR, Cook SA, Davisson MT (1996) Scrambler, a new neurological mutation of the mouse with abnormalities of neuronal migration. Mamm Genome 7: 798–802PubMedCrossRefGoogle Scholar
  46. Tang D, Yeung J, Lee KY, Matsushita M, Matsui H, Tomizawa K, Hatase O, Wang JH (1995) An isoform of the neuronal cyclin-dependent kinase 5 (CdkS) activator. J Biol Chem 270:26 897–26 903Google Scholar
  47. Tang D, Chun ACS, Zhang M, Wang JH (1997) Cyclin-dependent kinase 5 (CdkS) activation domain of neuronal CdkS activator. Evidence of the existence of cyclin fold in neuronal Cdk5a activator. J Biol Chem 272:12 318–12 327Google Scholar
  48. Tomizawa K, Matsui H, Matsushita M, Lew J, Tokuda M, Itano T, Konishi R, Wang JH, Hatase O (1996) Localization and developmental changes in the neuron-specific cyclin-dependent kinase 5 activator (p35nck5a) in the rat brain. Neuroscience 74: 519–529PubMedCrossRefGoogle Scholar
  49. Tsai LH, Takahashi T, Caviness VSJ, Harlow E (1993) Activity and expression pattern of cyclindependent kinase 5 in the embryonic mouse nervous system. Development 119: 1029–1040PubMedGoogle Scholar
  50. Tsai LH, Delalle I, Caviness VSJ, Chae T, Harlow E (1994) p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 371: 419–423Google Scholar
  51. Van den Heuvel S, Harlow E (1993) Distinct roles for cyclin-dependent kinases in cell cycle control. Science 262: 2050–2054PubMedCrossRefGoogle Scholar
  52. Ware ML, Fox JW, Gonzalez JL, Davis NM, Lambert de Rouvroit C, Russo CJ, Chua SC Jr, Goffinet AM, Walsh CA (1997) Aberrant splicing of a mouse disabled homolog, mdabl, in the scrambler mouse. Neuron 19: 239–249PubMedCrossRefGoogle Scholar
  53. Xiong W, Pestell R, Rosner MR (1997) Role of cyclins in neuronal differentiation of immortalized hippocampal cells. Mol Cell Biol 17: 6585–6597PubMedGoogle Scholar
  54. Zheng M, Leung CL, Liem RK (1998) Region-specific expression of cyclin-dependent kinase 5 (cdk5) and its activators, p35 and p39, in the developing and adult rat central nervous system. J Neurobiol 35: 141–159PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Young T. Kwon
  • Li-Huei Tsai
    • 1
  1. 1.Howard Hughes Medical Institute and the Department of PathologyHarvard Medical SchoolBostonUSA

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