Biotecnologia Aplicada Elfos Scientiae ISSN: 0684-4551 Vol. 13, Num. 1, 1996

Regulation of embryonic development by the proliferating cell nuclear antigen (pcna)

William R. Jeffery

Section of Molecular and Cellular Biology, University of California, Davis, U.S.A.

Code Number:BA96012
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Localized maternal RNAs control the specification of regional and cell fate during embryogenesis. However, little is known about how cell proliferation is coupled to the regional specification processes. We have investigated this problem in the ascidian embryo: a model system for studying the role of localized egg-cytoplasmic factors in embryonic development. The myoplasm, a localized egg-cytoplasmic region, contains the non-coding yellow crescent (YC) RNA. Sense probes containing the 3' region of YC RNA hybridize to other RNAs.

A cDNA library from the ascidian Styela clava was screened with YC probes to identify these RNAs. The screen resulted in the isolation of a clone encoding the ascidian proliferating cell nuclear antigen (PCNA). PCNA is a DNA polymerase co-factor that is required for DNA replication and repair in plant and animal cells. The PCNA mRNA has a long 3' UTR containing a 521 nucleotide sequence that is complementary to a virtually identical sequence in the 3' region of YC RNA. The PCNA and YC genes are single copy and overlap in their 3' regions on opposite strands of genomic DNA. The ascidian PCNA protein is 61, 69, and 71 4202500 identical to the Drosophila, Xenopus, and human PCNA respectively.

S. clava embryos contain maternal and zygotic PCNA mRNAs. The maternal PCNA mRNA is distributed throughout the egg, but it is depleted in the myoplasm. Immunolocalization with PCNA antibody showed that PCNA protein has the same distribution as the PCNA mRNA. Maternal PCNA mRNA and protein are specifically enhanced in the ectoplasm, which is segregated to the rapidly-proliferating epidermal and neural cell lineages and depleted in the myoplasm, which is distributed to muscle and other cell lineages which undergo only a few cell divisions before differentiation.

Thus, regional cell proliferation during embryogenesis may be controlled by PCNA distribution and YC RNA may prevent PCNA accumulation in the myoplasm by serving as an antisense regulator of PCNA mRNA. Zygotic PCNA mRNA first appears at the neurula stage and peaks in tailbud embryos. Surprisingly, zygotic PCNA mRNA and protein is confined to the nervous system. PCNA expression after the neural cells have ceased to proliferate suggests that this protein may have a novel role in nervous system differentiation. Knockout of zygotic PCNA expression during embryogenesis leads to specific defects in development of the larval brain and spinal cord.

The results suggest that YC RNA may be an antisense regulator of PCNA mRNA, that embryonic cell proliferation may be controlled by the localization of maternal PCNA and that PCNA may have a novel role in neural development.

Copyright 1996 Elfos Scientiae