A cyclin-dependent kinase family member (PHOA) is required to link developmental fate to environmental conditions in Aspergillus nidulans.

We addressed the question of whether Aspergillus nidulans has more than one cyclin-dependent kinase gene and identified such a gene, phoA, encoding two PSTAIRE-containing kinases (PHOAM1 and PHOAM47) that probably result from alternative pre-mRNA splicing. PHOAM47 is 66% identical to Saccharomyces cerevisiae Pho85. The function of this gene was studied using phoA null mutants. It functions in a developmental response to phosphorus-limited growth but has no effect on the regulation of enzymes involved in phosphorus acquisition. Aspergillus nidulans shows both asexual and sexual reproduction involving temporal elaboration of different specific cell types. We demonstrate that developmental decisions in confluent cultures depend upon both the initial phosphorus concentration and the inoculation density and that these factors influence development through phoA. In the most impressive cases, absence of phoA resulted in a switch from asexual to sexual development (at pH 8), or the absence of development altogether (at pH 6). The phenotype of phoA deletion strains appears to be specific for phosphorus limitation. We propose that PHOA functions to help integrate environmental signals with developmental decisions to allow ordered differentiation of specific cell types in A.nidulans under varying growth conditions. The results implicate a putative cyclin-dependent kinase in the control of development.     

Developmental control of cell division in leech embryos

During embryogenesis, cell division must be spatially and temporally regulated with respect to other developmental processes. Leech embryos undergo a series of unequal and asynchronous cleavages to produce individually recognizable cells whose lineages, developmental fates and cell cycle properties have been characterized. Thus, leech embryos provide an opportunity to examine the regulation of cell division at the level of individual well-characterized cells within a community of different types of cells. Isolation of leech homologues of some of the highly conserved regulators of the cell division cycle, and characterization of their patterns of maternal and zygotic expression, indicate that the cell divisions of early leech embryos are regulated by cell type-specific mechanisms. These studies with leech embryos contribute to the emerging appreciation of the diverse mechanisms by which animals regulate cell division during early development.     

The early impact of genetics on our understanding of cell cycle regulation in Aspergillus nidulans

The application of genetic analysis was crucial to the rapid progress that has been made in cell cycle research. Ron Morris, one of the first to apply genetics to cell cycle research, developed Aspergillus nidulans into an important model system for the analysis of many aspects of cell biology. Within the area of cell cycle research, Ron's laboratory is noted for development of novel cell biological and molecular genetic approaches as well as seminal insights regarding the regulation of mitosis, checkpoint regulation of the cell cycle, and the role of microtubule-based motors in chromosome segregation. In this special edition of FGB dedicated to Ron Morris, and in light of the recent progress in fungal genomics, we review the outstanding contributions his work made to our understanding of mitotic regulation. Indeed, his efforts have provided many mutants and experimental tools along with the conceptual framework for current and future studies of mitosis in A. nidulans.     

An extra copy of nimEcyclinB elevates pre-MPF levels and partially suppresses mutation of nimTcdc25 in Aspergillus nidulans.

Previous work has shown that nimA encodes a cell cycle regulated protein kinase that is required along with the p34cdc2 histone H1 kinase (MPF) for mitosis in Aspergillus nidulans. We have now identified two other gene products required for mitosis in A.nidulans. nimT encodes a protein similar to the fission yeast cdc25 tyrosine phosphatase and is required for the conversion of pre-MPF to MPF and nimE encodes a B-type cyclin which is a subunit of MPF. A new genetic interaction between nimEcyclinB and nimTcdc25 type genes is reported. Increased copy number of nimEcyclinB can suppress mutation of nimTcdc25 and also lead to increased accumulation of tyrosine phosphorylated p34cdc2 (pre-MPF). This biochemical observation suggests an explanation for the genetic complementation. If nimEcyclinB recruits p34cdc2 for tyrosine phosphorylation to form pre-MPF it follows that increased expression of nimEcyclinB would increase the level of pre-MPF. The increased level of pre-MPF generated may then allow the mutant nimTcdc25 protein to convert enough pre-MPF to MPF and thus permit some mitotic progression. We also demonstrate that correct cell cycle regulation by the p34cdc2 protein kinase pathway is essential for correct developmental progression in A.nidulans.     

Asexual sporulation signalling regulates autolysis of Aspergillus nidulans via modulating the chitinase ChiB production

Aims:  Elucidation of the regulation of ChiB production in Aspergillus nidulans .
Methods and Results:  Mutational inactivation of the A. nidulans chiB gene resulted in a nonautolytic phenotype. To better understand the mechanisms controlling both developmental progression and fungal autolysis, we examined a range of autolysis-associated parameters in A. nidulans developmental and/or autolytic mutants. Investigation of disorganization of mycelial pellets, loss of biomass, extra-/intracellular chitinase activities, ChiB production and chiB mRNA levels in various cultures revealed that, in submerged cultures, initialization of autolysis and stationary phase-induced ChiB production are intimately coupled, and that both processes are controlled by the FluG-BrlA asexual sporulation regulatory pathway. ChiB production does not affect the progression of apoptotic cell death in the aging A. nidulans cultures.
Conclusions:  The endochitinase ChiB plays an important role in autolysis of A. nidulans , and its production is initiated by FluG-BrlA signalling. Despite the fact that apoptosis is an inseparable part of fungal autolysis, its regulation is independent to FluG-initiated sporulation signalling.
Significance and Impact of the Study:  Deletion of chiB and fluG homologues in industrial filamentous fungal strains may stabilize the hyphal structures in the autolytic phase of growth and limit the release of autolytic hydrolases into the culture medium.     

Geminin Coordinates Cell Cycle and Developmental Control

Growth and differentiation are two major themes in embryonic development. Numerous cell divisions have to be regulated on the path from a unicellular embryo, the zygote, to the multicellular structures of a mature being. Numerous functions, specializations and cellular identities have to be generated, in order to form a complex and mature animal. Numerous mechanisms have to control the correct assignment and acquisition of cellular fates, as well as the right timing and allocation of cells. Therefore, a strict coordination has to occur between embryonic patterning and the cell cycle. From this point of view, dual roles or mutual interactions of typical proliferation and developmental control genes are likely. Recently, new light was shed on these issues by identifying the nuclear protein Geminin as a molecular coordinator between the cell cycle and axial patterning. We summarize the role of Geminin in cell cycle, in the embryonic patterning controlled by Hox genes, providing insights into cell cycle regulators in embryonic development, and, conversely, typical developmental control genes in cell cycle regulation.     

Early pattern formation in the developing Drosophila eye

The formation of complex cellular arrays from unpatterned epithelia is a widespread developmental phenomenon. Insights into the mechanisms regulating this transformation have come from studying the development of the Drosophila compound eye. Pattern formation in the eye primordium is a highly ordered process in which the onset of differentiation is coordinated with synchronization of cell cycle progression. Recent studies have identified a number of genes that are required for early patterning events, and provide a link between the regulation of proliferation and pattern formation.     

Cell cycle and differentiation

The development of multicellular organisms relies on the temporal and spatial control of cell proliferation and cell growth. The relationship between cell-cycle progression and development is complex and characterized by mutual dependencies. On the level of the individual cell, this interrelationship has implications for pattern formation and cell morphogenesis. On a supercellular level, this interrelationship affects meristem function and organ growth. Often, developmental signals not only direct cell-cycle progression but also set the frame for cell-cycle regulation by determining cell-type-specific cell-cycle modes. In other cases, however, cell-cycle progression appears to be required for the further differentiation of some cell types. There are also examples in which cell cycle and differentiation seem to be controlled at the same level and progress rather independently from each other or are linked by the same regulator or pathway. Furthermore, different relationships between cell cycle and differentiation can be combined in a succession of events during development, leading to complex developmental programs.     

Calmodulin and cell cycle control.

Previous studies have indicated a role for the calcium receptor calmodulin in the control of eukaryotic cell proliferation. Using a molecular genetic approach in the filamentous fungus Aspergillus nidulans we have shown that CaM is required for cell cycle progression at multiple points in the cell cycle. Construction of an A nidulans strain conditional for calmodulin expression reveals that this protein is required during G1/S and for the initiation of mitosis. A lack of calmodulin results in cell cycle arrest, and a failure in polar growth that accompanies germination of A nidulans spores. In addition, increased expression of calmodulin in this organism permits growth at suboptimal calcium concentrations, indicating that cell growth is coordinately regulated by calcium and calmodulin. Together these results indicate that calmodulin-dependent processes may be conserved between A nidulans and vertebrate cells, and suggest that this approach may allow us to elucidate the molecular mechanism underlying calmodulin-regulated control of cell proliferation.