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J A Knoblich

Publications and source records attributed to J A Knoblich.

25 records · Page 2Linked to original sources
PubMed1995

Asymmetric segregation of Numb and Prospero during cell division.

A cell can divide asymmetrically by specifically segregating a determinant into one of its daughter cells. The Numb protein is a candidate for such a determinant in the asymmetric cell divisions of the developing Drosophila nervous system. Numb is a membrane-associated protein that localizes asymmetrically during cell division and segregates into one daughter cell, where it is required for the specification of the correct cell fate. Here we show that a nuclear protein, Prospero, translocates to the membrane at the beginning of cell division and colocalizes with Numb throughout mitosis, suggesting a common mechanism for asymmetric segregation. Numb and Prospero localization is coupled to mitosis and tightly correlated with the position of one of the two centrosomes. In contrast to centrosome positioning, however, Numb and Prospero localization is independent of microtubules. Cytochalasin D treatment suggests that the process is also independent of actin. We propose that there is an organizer of asymmetric cell division which provides positional information for both the orientation of the mitotic spindle and asymmetric localization of Numb and Prospero.

Actins↗
PubMed1995

Distinct modes of cyclin E/cdc2c kinase regulation and S-phase control in mitotic and endoreduplication cycles of Drosophila embryogenesis.

Drosophila cyclin E (DmcycE) is required in embryos for S phase of mitotic and endoreduplication cycles. Here, we describe regulatory differences characteristic for these two cell cycle types. While DmcycE transcript levels decline in DmcycE mutant cells programmed for mitotic proliferation, they are maintained and no longer restricted to transient pulses in DmcycE mutant cells programmed for endoreduplication. Moreover, DmcycE expression in endoreduplicating cells is down-regulated by ectopic expression of a heat-inducible cyclin E transgene. DmcycE expression in endoreduplicating tissues, therefore, is restricted by a negative feedback to the transient pulse triggering entry into S-phase. Conversely, during mitotic cycles, where S phase entry is not only dependent on cyclin E but also on progression through M phase, cyclin E and associated Dmcdc2c kinase activity are present throughout the cell cycle. Reinitiation of DNA replication during the G2 phase of the mitotic cell cycle, therefore, is prevented by cyclin E/Dmcdc2c kinase-independent regulation. Observations in cyclin A mutants implicate G2 cyclins in this regulation. Our results suggest molecular explanations for the different rules governing S phase during mitotic and endoreduplication cycles.

Animals↗
PubMed1995

Caenorhabditis elegans cyclin A- and B-type genes: a cyclin A multigene family, an ancestral cyclin B3 and differential germline expression.

We have cloned cDNAs for Caenorhabditis elegans cyclins A1, B and B3. While cyclins A1 and B are most closely related to either A- or B-type cyclins of other species, cyclin B3 is less related to these cyclins. However, this cyclin is most similar to the recently identified chicken cyclin B3. Our identification of a Caenorhabditis homolog demonstrates that cyclin B3 has been conserved in evolution. Cyclin A1 is a member of an A-type multigene family; however the cyclin A1 cDNA only recognizes a single band on northern blots. A single-sized RNA is also observed for the cyclin B3 cDNA. In contrast, three different transcripts are observed for the cyclin B cDNA. Based on our analyses using RNAs from germline-defective mutants and from populations enriched for males, one cyclin B transcript is specific to the paternal germline. The two other cyclin B transcripts, as well as the cyclin A1 and cyclin B3 transcripts, are most abundant in the maternal germline and are only present at low levels in other tissues. Moreover, the 3' untranslated regions of each Caenorhabditis cyclin cDNA possess several copies of potential translational control elements shown in Xenopus and Drosophila maternal cyclin mRNAs to function during oogenesis and early embryogenesis.

Amino Acid Sequence↗
PubMed1994

Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation.

Most cells of the dorsal epidermis exit from the mitotic cycle after division 16 in Drosophila embryogenesis. This exit is dependent on the down-regulation of Drosophila cyclin E (DmcycE) during the final mitotic cycle. Ectopic expression of DmcycE after the final mitosis induces entry into S phase and reaccumulation of G2 cyclins and results in progression through a complete additional cell cycle. Conversely, analyses in DmcycE mutant embryos indicate that cyclin E is required for progression through S phase of the mitotic cycle. Moreover, endoreplication, which occurs in late wild-type embryos in the same pattern as DmcycE expression, is not observed in the mutant embryos. Therefore, Drosophila cyclin E, which forms a complex with the Dmcdc2c kinase, controls progression through S phase and its down-regulation limits embryonic proliferation.

Animals↗
PubMed1993

Synergistic action of Drosophila cyclins A and B during the G2-M transition.

A variety of different cyclin proteins have been identified in higher eukaryotes. In the case of cyclin B, functional analyses have clearly demonstrated an important role in the control of entry into mitosis. The function of cyclin A is more complex. It appears to function in the control of both S- and M-phase. The results of our genetic analyses in Drosophila demonstrate that cyclin A has a mitotic function and that it acts synergistically with cyclin B during the G2-M transition. In double mutant embryos that express neither cyclin A nor cyclin B zygotically, cell cycle progression is blocked just before the exhaustion of the maternally contributed cyclin A and B stores. BrdU-labeling experiments indicate that cell cycle progression is blocked in G2 before entry into the fifteenth round of mitosis. Expression of either cyclin A or B from heat-inducible transgenes is sufficient to overcome this cell cycle block. This block is also not observed in single mutant embryos deficient for either cyclin A or B. In cyclin B deficient embryos, cell cycle progression continues after the apparent exhaustion of the maternal contribution, suggesting that cyclin B might not be essential for mitosis. However, mitotic spindles are clearly abnormal and progression through mitosis is delayed in these cyclin B deficient embryos.

Animals↗
PubMed1992

Cyclins and cdc2 kinases in Drosophila: genetic analyses in a higher eukaryote.

Cyclin proteins and the kinases with which they associate are encoded by gene families in multicellular eukaryotes. A variety of cyclin/kinase complexes with different functions may exist. We have started a genetic dissection of this complexity in Drosophila. We have done experiments to investigate a potential functional overlap between two kinases (Dmcdc2 and Dmcdc2c) and two cyclins (cyclin A and cyclin B). No functional overlap was observed between the Dmcdc2 and the Dmcdc2c kinases. The phenotype resulting from mutations in Dmcdc2 was not affected by altering the level of Dmcdc2c. Our results concerning cyclin A and cyclin B strongly suggest that these two cyclins have largely overlapping functions. Cell proliferation was observed in the absence of either cyclin A or cyclin B, but not if both cyclins were absent. Cyclin A also has essential functions that cannot be taken over by cyclin B, but these functions appear to be required at defined developmental stages in specific tissues only.

Animals↗