Biomedical subjects

B A Edgar

Publications and source records attributed to B A Edgar.

9 recordsLinked to original sources

PubMed1990

The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string.

The string (stg) locus of Drosophila encodes a factor that is thought to trigger mitosis by activating the p34cdc2 protein kinase. stg is required for mitosis early in development and is transcribed in a dynamic pattern that anticipates the pattern of embryonic cell divisions. Here we show that differential cell cycle regulation during postblastoderm development (cell cycles 14-16) occurs in G2. We demonstrate that stg mRNA expressed from a heat shock promotor triggers mitosis, and an associated S phase, in G2 cells during these cycles. Hence, differential cell cycle timing at this developmental stage is controlled by stg. Finally, we use heat-induced stg expression to alter the normal pattern of embryonic mitoses. Surprisingly, the complex mitotic pattern evident during normal development is not essential for many features of pattern formation or for viability.

Animals↗

PubMed1989

Directing cell division during development.

Several evolutionarily conserved proteins constitute a universal mitotic trigger that is precisely controlled during the orderly cell divisions of embryogenesis. As development progresses, the mechanisms controlling this trigger change. Early divisions are executed by maternally synthesized gene products, and in Xenopus they are timed by the accumulation and periodic degradation of cyclin, a trigger component. Later, the zygotic genome assumes control, and in Drosophila, zygotic transcription is required for production of another trigger protein, the product of string. After this transition to zygotic control, pulses of string transcription define the timing of highly patterned embryonic cell divisions and cyclin accumulation is not rate limiting.

Animals↗

PubMed1989

Genetic control of cell division patterns in the Drosophila embryo.

In Drosophila embryogenesis, mitotic control undergoes a significant transition during the 14th interphase. Mitoses before interphase 14 run on maternal products, and occur in metasynchronous waves. Mitoses after interphase 14 require zygotic transcription, and occur asyncronously in an intricate, highly ordered spatio-temporal pattern. Mutations at the string (stg) locus cause cell-cycle arrest during this transition, in G2 of interphase 14, yet do not arrest other aspects of development. This phenotype suggests that stg is required specifically for initiating mitosis. We describe the cloning of stg, and show that its predicted amino acid sequence is homologous to that of cdc25, a regular of mitotic initiation in the yeast S. pombe. In addition, we show that zygotic expression of stg mRNA occurs in a dynamic series of spatial patterns which anticipate the patterns of the zygotically driven cell divisions. Therefore we suggest that regulated expression of stg mRNA controls the timing and location of these embryonic cell divisions.

Amino Acid Sequence↗

PubMed1989

A genetic switch, based on negative regulation, sharpens stripes in Drosophila embryos.

The pair-rule genes hairy, runt, even-skipped, and fushi tarazu express their mRNAs and proteins in striped patterns in the Drosophila embryo at the blastoderm stage. Previous studies have shown that the generation of these patterns depends upon products of the gap genes and upon interactions between the pair-rule genes themselves. Here we show that blocking protein synthesis induces expression of each of the pair-rule mRNAs in virtually all regions of the embryo. Our observations together with genetic studies carried out in other laboratories suggest that negative feedback between the pair-rule genes plays a key role in striped expression of pair-rule genes. We propose that stable proteins, present in all regions of the embryo, first activate transcription of these pair-rule genes constitutively. Then, various combinations of unstable proteins repress their transcription in a patterned fashion; each stripe of accumulated products of a given pair-rule gene marks a region where it was not repressed. We develop this idea in mathematical form and demonstrate that a network of mutual repression by pair-rule genes can make each blastoderm nucleus into a genetic switch with two stable states. If preexisting gap gene patterns provide initial bias to the blastoderm nuclei, then the "bistable switch behavior" of the nuclei can refine an initially weak spatial bias into a final pattern of sharp stripes.

Animals↗

PubMed1988

Spatial regulation of engrailed expression in the Drosophila embryo.

Novel patterns of engrailed RNA were observed in early Drosophila embryos injected with cycloheximide, an inhibitor of protein synthesis. From these patterns, we infer that there are several superimposed systems of spatial regulation which in combination localize engrailed expression in the embryo. Activation of engrailed transcription progresses with an anterior-to-posterior polarity. Superimposed are systems of negative regulation that repress expression in the anterior 30% of the embryo and in the interbands between stripes. We suggest that products of known segmentation genes are the repressors that suppress engrailed expression in interbands.

Animals↗

PubMed1987

Cytoarchitecture and the patterning of fushi tarazu expression in the Drosophila blastoderm.

In the Drosophila embryo at the blastoderm stage, the segmentation gene fushi tarazu (ftz) is expressed in a seven-banded pattern. The generation of this pattern, like many other segmentation gene expression patterns, coincides with the formation of cell membranes around the blastoderm nuclei. To test the role of cellularization in resolving the banded ftz pattern, we used cytoskeletal inhibitors (colcemid and cytochalasin B) to block cellularization. We found that banded ftz RNA and protein patterns can form without cellular structure. We also tested the importance of rapid degradation of the ftz RNA, using cycloheximide to block degradation. RNA degradation is essential to maintain the banded ftz pattern in a syncytium, but is not required to maintain the pattern in a cellularized embryo. A latticework of cytoskeletal microtubules that forms during cellularization appears to be a key component in localizing the ftz mRNA. We conclude that RNA degradation and cellular structure normally work together to localize ftz RNA to its sites of synthesis.

Animals↗

PubMed1986

Repression and turnover pattern fushi tarazu RNA in the early Drosophila embryo.

Embryonic expression of transcripts from the Drosophila gene fushi tarazu (ftz) progresses through a series of spatial patterns, culminating in a seven-banded pattern at the cellular blastoderm stage. We studied the generation of this pattern using inhibitors of RNA synthesis (alpha-amanitin) and protein synthesis (cycloheximide). Injections of alpha-amanitin revealed that ftz RNA turns over extremely rapidly in the embryo, and we think that this may be essential to effect rapid changes in ftz RNA patterns. Injections of cycloheximide added to the normal domains of ftz expression, creating novel expression patterns that were dependent on the time of injection. These novel patterns suggest that two superimposed systems of repression establish the normal, seven-banded pattern of ftz expression. One system sets up a banded pattern over the entire length of the embryo, and the other restricts actual expression to the middle portion of the embryo.

Amanitins↗

PubMed1986

Parameters controlling transcriptional activation during early Drosophila development.

We studied transcription during the first 14 mitotic cycles of Drosophila development, by gel electrophoresis of RNA pulse-labeled in vivo. Synthesis of rRNA, tRNAs, 5S RNAs, snRNAs, poly(A)+ RNAs, and histone mRNAs is first detectable during cycle 11 or 12. Histone genes are transcribed during S phases, and reach maximal activation in cycle 12, whereas nonhistone genes are transcribed only in G2 periods, and reach maximal activation during late cycle 14. The high transcriptional activity characteristic of cycle 14 can be precociously induced by extending interphase with cycloheximide as early as, but not before, cycle 10. We conclude that all classes of genes become competent for activation during cycle 10, and that subsequent activation is differentially suppressed by functions associated with nuclear division.

Animals↗

PubMed1986

Cell cycle control by the nucleo-cytoplasmic ratio in early Drosophila development.

We have studied the role of the nucleo-cytoplasmic ratio in the early development of Drosophila, using mutants and experimental manipulations that alter nuclear density. Haploid embryos produced by either maternal or paternal effect mutations compensate for haploidy by an extra nuclear division during the syncytial blastoderm stage. Decreasing the nucleo-cytoplasmic ratio in wild-type embryos by ligation can cause a similar extra blastoderm division. Conversely, increasing this ratio can cause the omission of a blastoderm division. The duration of mitotic cycles is affected by the nucleo-cytoplasmic ratio four cycles before the terminal blastoderm division. Transcription patterns in haploid embryos indicate that transcriptional activation is not directly controlled by the nucleo-cytoplasmic ratio, but may be an effect of the lengthening of interphase periods.

Animals↗