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D Solter

Publications and source records attributed to D Solter.

At least 19 recordsLinked to original sources
PubMed2004

Systems biology of the 2-cell mouse embryo.

The transcriptome of the 2-cell mouse embryo was analyzed to provide insight into the molecular networks at play during nuclear reprogramming and embryonic genome activation. Analysis of ESTs from a 2-cell cDNA library identified nearly 4,000 genes, over half of which have not been previously studied. Transcripts of mobile elements, especially those of LTR retrotransposons, are abundantly represented in 2-cell embryos, suggesting their possible role in introducing genomic variation, and epigenetic restructuring of the embryonic genome. Analysis of Gene Ontology of the 2-cell-stage expressed genes outlines the major biological processes that guide the oocyte-to-embryo transition. These results provide a foundation for understanding molecular control at the onset of mammalian development.

Animals↗
PubMed2001

Expression of genes involved in mammalian meiosis during the transition from egg to embryo.

The ooplasm of higher eukaryotes provides substances necessary for completing the last stages of meiosis and initiating the first mitotic division. These processes are firmly attuned to other events in the egg and newly formed embryo, such as switching from the use of maternal transcripts to the onset of zygotic transcription. In mammals little is known about the molecular mechanisms guiding this transition, largely due to the lack of information about genes expressed in the egg and early embryos. Studies of yeast mitosis have contributed much of what is known about the vertebrate cell cycle, and recent reports indicate that homologs of yeast DNA repair genes also function during mammalian gametogenesis. To examine whether this conservation can be expanded to include genes operative in oocyte meiosis, we performed a computer-based search for homologs of yeast genes that are induced during sporulation in C. elegans, Drosophila, and mammals. Results from this study suggest that yeast and higher eukaryotes share genes that coordinate the overall process of meiosis. However intriguing differences exist, reflecting the distinctive mechanisms governing the progression of meiosis in each organism. ESTs representing more than half of the mammalian homologs are present in mouse cDNA libraries that contains genes controlling the meiosis/mitosis transition. About 50% of these genes contain potential cis-elements for cytoplasmic polyadenylation in their 3'-UTR, suggesting the importance of controlled translation in the egg and zygote.

Animals↗
PubMed2000

Mammalian cloning: advances and limitations.

For many years, researchers cloning mammals experienced little success, but recent advances have led to the successful cloning of several mammalian species. However, cloning by the transfer of nuclei from adult cells is still a hit-and-miss procedure, and it is not clear what technical and biological factors underlie this. Our understanding of the molecular basis of reprogramming remains extremely limited and affects experimental approaches towards increasing the success rate of cloning. Given the future practical benefits that cloning can offer, the time has come to address what should be done to resolve this problem.

Animals↗
PubMed2000

Timely translation during the mouse oocyte-to-embryo transition.

In the mouse, completion of oocyte maturation and the initiation of preimplantation development occur during transcriptional silence and depend on the presence and translation of stored mRNAs transcribed in the growing oocyte. The Spin gene has three transcripts, each with an identical open reading frame and a different 3' untranslated region (UTR). (Beta)-galactosidase-tagged reporter transcripts containing each of the different Spin 3'UTRs were injected into oocytes and zygotes and (beta)-galactosidase activity was monitored. Results from these experiments suggest that differential polyadenylation and translation occurs at two critical points in the oocyte-to-embryo transition - upon oocyte maturation and fertilization - and is dependent on sequences in the 3'UTR. The stability and mobility shifts of ten other maternal transcripts were monitored by reprobing a northern blot of oocytes and embryos collected at 12 hour intervals after fertilization. Some are more stable than others and the upward mobility shift associated with polyadenylation correlates with the presence of cytoplasmic polyadenylation elements (CPEs) within about 120 nucleotides of the nuclear polyadenylation signal. A survey of the 3' UTRs of expressed sequence tag clusters from a mouse 2-cell stage cDNA library indicates that about one third contain CPEs. We suggest that differential transcript stability and a translational control program can supply the diversity of protein products necessary for oocyte maturation and the initiation of development.

3' Untranslated Regions↗
PubMed1999

Expression of Melk, a new protein kinase, during early mouse development.

A new gene named maternal embryonic leucine zipper kinase, Melk, has been recently identified (Heyer et al. [1997] Mol. Reprod. Dev. 47:148-156). As a basis for further study of the function of the gene, we have examined the expression of Melk across a wide range of embryonic stages, from the ovulated egg and 2-cell embryo through the gastrulation and early organogenesis stages, by in situ hybridization and immunohistochemistry. Melk is expressed in a spatially and temporally specific pattern during mammalian embryogenesis. The strongest expression was detected during maturation of oocytes and preimplantation development. Given its expression pattern, Melk may play an important role during preimplantation embryonic development. Dev Dyn 1999;215:344-351.

Animals↗
PubMed1999

The mouse cornichon gene family.

As part of a large scale mouse Expressed Sequence Tag (EST) project to identify molecules involved in the initiation of mammalian development, a homolog of the Drosophila cornichon gene was detected as a mouse maternal transcript present in the two-cell embryo. Cornichon is a multigene family in the mouse: the new gene, Cnih, maps to mouse chromosome 10, another cornichon homolog, Cnil, maps to chromosome 14 and two additional cornichon-related loci, possibly pseudogenes, localize to chromosomes 3 and 10, respectively. Cnih encodes an open reading frame (ORF) of 144 amino acids that is 93% homologous (68% identical) to the Drosophila protein, whereas the ORF of Cnil contains two extra polypeptide regions not found in these other proteins. Transcripts of Cnih are highly abundant in the full grown oocyte and the ovulated unfertilized egg, while Cnil message is only detectable after activation of the embryonic genome at the eight-cell stage. In situ hybridization shows specific localization of Cnih transcripts to ovarian oocytes. The lack of cytoplasmic polyadenylation of the maternally inherited Cnih transcript suggests that Cnih mRNA is translated in the full grown oocyte before, but not after, ovulation. In Drosophila, cornichon is involved in the establishment of both anterior-posterior and dorso-ventral polarity via the epidermal growth factor (EGF)-receptor signaling pathway. Finding Cnih in the mammalian oocyte opens a new perspective on the investigation of EGF-signaling in the oocyte.

Amino Acid Sequence↗
PubMed1999

Cloning and embryonic stem cells: a new era in human biology and medicine.

The cloning of mammals using adult cells as nuclear donors has been achieved and the same procedure can be, at least theoretically, used to clone humans. Another recent technological advance, the derivation of human embryonic stem cells, opens up new possibilities in cell and tissue replacement therapy and heralds significant improvements in gene therapy. Besides suggesting new and potentially valuable medical applications, the insights gained through the use of these techniques could significantly enrich our understanding of basic mechanisms regulating human development. On the other hand, these preliminary results are viewed by many as the opening of the Pandora's box and there are loud voices clamoring that research in these areas be forbidden in perpetuity. I suggest in the following article that at present we do not know enough to make anything but an entirely emotional decision about future applications of these techniques. I try to summarize the current state of the kn owledge in the field and indicate how much further research is necessary if benefits and drawbacks are to be properly understood.

Animals↗
PubMed1998

SPIN, a substrate in the MAP kinase pathway in mouse oocytes.

The newly cloned gene Spin encodes a 30-kDa protein, a well-defined abundant molecule found in mouse oocytes and early embryos. This protein SPIN undergoes metaphase-specific phosphorylation and binds to the spindle. To understand the role of SPIN in oocyte meiosis, oocytes were treated with drugs that affect the cell cycle by activating or inactivating specific kinases. The posttranslational modification of SPIN in the treated oocytes was then investigated by one- and two-dimensional gel electrophoresis. Modification of SPIN is inhibited by treatment with 6-dimethylaminopurine (DMAP), suggesting that SPIN is phosphorylated by a serine-threonine kinase. Furthermore, SPIN from cycloheximide-treated oocytes that lack detectable MAP kinase activity is only partially phosphorylated, indicating that SPIN may be phosphorylated by the MOS/MAP kinase pathway. To confirm this observation, SPIN was analyzed in Mos-null mutant mice lacking MAP kinase activity. Normal posttranslational modification of SPIN did not occur in Mos-null mutant oocytes. In addition, there is reduced association of SPIN with the metaphase I spindle in Mos-null mutant oocytes, as determined by immunohistochemical analysis. These findings suggest that SPIN is a substrate in the MOS/ MAP kinase pathway and further that this phosphorylation of SPIN may be essential for its interaction with the spindle.

Adenine↗
PubMed1998

Imprinting.

Imprinting provides a fascinating mechanism of control of gene expression so that the maternal and paternal alleles of some genes are unequally expressed. Imprinting is most likely established during gametogenesis by a mechanism not completely clear, though DNA methylation probably plays a certain role. Expression of imprinted gene significantly affects mammalian development so that only the maternal or only the paternal diploid genomes cannot support normal development. Since imprinting results in functional hemizygocity, mutation of the expressed allele can have the drastic consequences of a null mutation. For this reason identification of imprinted genes and further understanding of the imprinting mechanism represent an important change for human medical genetics.

Animals↗
PubMed1997

Maid: a maternally transcribed novel gene encoding a potential negative regulator of bHLH proteins in the mouse egg and zygote.

We isolated an abundant novel cDNA SSEC-8 from a subtraction cDNA library enriched for maternal transcripts that are still present in the mouse 2 cell stage embryo. This gene is evolutionarily conserved and maps to the distal region of mouse chromosome 2. The deduced polypeptide sequence of the encoded protein contains a conserved helix-loop-helix (HLH) motif without a basic DNA binding domain, suggesting that it functions as a negative regulator of basic (b) HLH transcription factors. Gel mobility shift assays show that in vitro translated protein prevents the E12/MyoD bHLH dimer from binding to DNA. Also, transient overexpression of this protein in C2C12 cells reduced the transcription of a CAT-reporter regulated by an E12/MyoD driven enhancer. The 3'-UTR contains consensus sequences of cytoplasmic polyadenylation elements (CPE's), and the length of its poly (A) tail changes during oocyte maturation, indicating that its expression is controlled by timely activation of translation. This new gene, Maid, models the translational and transcriptional regulation of gene expression during the transition from gamete to embryo.

Amino Acid Sequence↗