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Molecular and Cellular Biology, July 2002, p. 4863-4875, Vol. 22, No. 13
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.13.4863-4875.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cyclin D and cdk4 Are Required for Normal Development beyond the Blastula Stage in Sea Urchin Embryos

Jennifer C. Moore,1,2 Jan L. Sumerel,1,2 Bradley J. Schnackenberg,1 Jason A. Nichols,1,3 Athula Wikramanayake,4 Gary M. Wessel,5 and William F. Marzluff1,2,3*

Program in Molecular Biology and Biotechnology,1 Department of Biochemistry and Biophysics,2 Department of Biology University of North Carolina, Chapel Hill, North Carolina 27599;,3 Department of Zoology, University of Hawaii, Honolulu, Hawaii 96822,4 Department of Molecular Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 029125

Received 9 October 2001/ Returned for modification 13 November 2001/ Accepted 28 March 2002

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.

* Corresponding author. Mailing address: Program in Molecular Biology and Biotechnology, CB# 7100, University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 962-8920. Fax: (919) 966-6821. E-mail: marzluff{at}med.unc.edu.

Molecular and Cellular Biology, July 2002, p. 4863-4875, Vol. 22, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.13.4863-4875.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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