title: G1/S phase cyclin-dependent kinase overexpression perturbs early development and delays tissue-specific differentiation in Xenopus.
abstract: Cell division and differentiation are largely incompatible but the molecular links between the two processes are poorly understood. Here, we overexpress G1/S phase cyclins and cyclin-dependent kinases in Xenopus embryos to determine their effect on early development and differentiation. Overexpression of cyclin E prior to the midblastula transition (MBT), with or without cdk2, results in a loss of nuclear DNA and subsequent apoptosis at early gastrula stages. By contrast, overexpressed cyclin A2 protein does not affect early development and, when stabilised by binding to cdk2, persists to tailbud stages. Overexpression of cyclin A2/cdk2 in post-MBT embryos results in increased proliferation specifically in the epidermis with concomitant disruption of skin architecture and delay in differentiation. Moreover, ectopic cyclin A2/cdk2 also inhibits differentiation of primary neurons but does not affect muscle. Thus, overexpression of a single G1/S phase cyclin/cdk pair disrupts the balance between division and differentiation in the early vertebrate embryo in a tissue-specific manner.
authors.affiliation: Department of Oncology, Cambridge University, Hutchison/MRC Research Centre, Addenbrookes Hospital, Hills Road, Cambridge CB2 2XZ, UK. ap113@cam.ac.uk
authors.forename: Laurent
authors.initials: L
authors.lastname: Richard-Parpaillon
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Cosgrove
authors.forename: Christine
authors.initials: C
authors.lastname: Devine
authors.forename: Ann E
authors.initials: AE
authors.lastname: Vernon
authors.forename: Anna
authors.initials: A
authors.lastname: Philpott
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D036703:Blastula / Q000166:cytology; D042846:CDC2-CDC28 Kinases / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology; D016193:G1 Phase / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000166:cytology; D009928:Organ Specificity; D016196:S Phase / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
chemical_list: C503725:CCNA2 protein, Xenopus; D019925:Cyclin A; D019927:Cyclin E; D029867:Xenopus Proteins; D042846:CDC2-CDC28 Kinases; C495891:Cdk2 protein, Xenopus; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases