Regulation of Morphogenesis and Multicellular Development in Aspergillus Grant uri icon



  • Multicellular development in eukaryotes requires precise integration of a
    number of fundamental biological processes. Environmental or intrinsic
    factors can activate diverse signal transduction pathways that elicit
    tissue- or developmental-specific morphogenesis. Orderly differentiation
    and spatial organization of diverse cell types frequently requires that
    regulation of cell-specific gene expression be coupled to alterations in
    cell cycle regulation. Ultimately, cellular morphogenesis is driven by
    changes in basic processes controlling cell growth, polarity, and asymmetry
    in cell division. The long-term goal of this project is to address
    mechanistic questions concerning multicellular development and tissue
    formation using the filamentous fungus Aspergillus nidulans. As in higher
    eukaryotes, external and internal signals induce two highly synchronous
    developmental events. Asexual reproduction (conidiation) is characterized
    by the spatiotemporal organization of a limited number of differentiated
    cell types. Complex transcriptional regulatory interactions coordinate the
    expression of hundreds of cell-specific genes with critical changes in cell
    cycle regulation. A conidiation-independent set of regulatory interactions
    controls both tissue formation during sexual reproduction and cell cycle
    modifications required during gametogenesis. The objectives of this
    proposal are directed toward elucidating mechanisms that control
    multicellular development during conidiation, regulate gametogenesis and
    sexual tissue development, and integrate these two reproductive processes.
    Specific objectives are focused upon a molecular analysis of the Medusa
    (medA), Stunted (stuA) and AnSterile12 (anste12) genes. MedAp is required
    for commitment to the developmental program, functioning as a co-activator
    of a subset of conidiation-specific genes and of unknown function in
    gametogenesis. StuAp is an APSES-domain protein that is an essential
    component in integrating developmental gene expression and cell cycle
    regulation. The homeodomain protein AnSte12p is related to fungal proteins
    known to play essential roles in converting distinct signal transduction
    inputs into specific developmental events. A balance between functions of
    StuAp, MedAp and AnSte12p with other developmental regulators establishes
    cell-specific morphology in Aspergillus nidulans.

    During the proposed funding period a series of interrelated classical
    genetic, molecular genetic and biochemical experiments are designed to: 1)
    identify DNA response elements within an upstream enhancer required for
    developmentally regulated, but BrlAp-, AbaAp-independent expression of
    stuA; 2) begin characterization of novel regulatory factors that bind
    these response elements; 3) determine if stuA overexpression alone, or in
    combination with brlA, alters the cell cycle through modification of G1/S
    and/or G2/M checkpoints; 4) continue characterization of extragenic
    suppressors of stuA mutations and extragenic mutations that mimic the
    stunted phenotype; 5) functionally characterize MedAp - is it a novel
    sequence-specific DNA binding protein?; 6) isolate extragenic mutations
    that suppress medA -induced growth arrest; 7) physically characterize the
    A. nidulans ste12 homolog and begin analysis of the biological role of
    AnSte12p in Aspergillus development. These experiments should provide
    important insights into similar mechanisms operating in dimorphic fungi as
    well as regulatory features that distinguish homothallic and heterothallic
    fungi. These experiments should also provide a greater understanding of
    the diverse strategies used to direct eukaryotic cell differentiation and
    responses to environmental factors.

date/time interval

  • April 15, 1999 - March 31, 2004

total award amount

  • 356,060