title: Cyclin D and cdk4 are required for normal development beyond the blastula stage in sea urchin embryos.
abstract: cdk4 mRNA and protein are constitutively expressed in sea urchin eggs and throughout embryonic development. In contrast, cyclin D mRNA is barely detectable in eggs and early embryos, when the cell cycles consist of alternating S and M phases. Cyclin D mRNA increases dramatically in embryos at the early blastula stage and remains at a constant level throughout embryogenesis. An increase in cdk4 kinase activity occurs concomitantly with the increase in cyclin D mRNA. Ectopic expression of cyclin D mRNA in eggs arrests development before the 16-cell stage and causes eventual embryonic death, suggesting that activation of cyclin D/cdk4 in cleavage cell cycles is lethal to the embryo. In contrast, blocking cyclin D or cdk4 expression with morpholino antisense oligonucleotides results in normal development of early gastrula-stage embryos but abnormal, asymmetric larvae. These results suggest that in sea urchins, cyclin D and cdk4 are required for normal development and perhaps the patterning of the developing embryo, but may not be directly involved in regulating entry into the cell cycle.
authors.affiliation: Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Moore
authors.forename: Jan L
authors.initials: JL
authors.lastname: Sumerel
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Schnackenberg
authors.forename: Jason A
authors.initials: JA
authors.lastname: Nichols
authors.forename: Athula
authors.initials: A
authors.lastname: Wikramanayake
authors.forename: Gary M
authors.initials: GM
authors.lastname: Wessel
authors.forename: William F
authors.initials: WF
authors.lastname: Marzluff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001755:Blastocyst; D003001:Cloning, Molecular; D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016213:Cyclins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012617:Sea Urchins / Q000196:embryology* / Q000235:genetics
chemical_list: D056741:Cyclin D; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases