DEVELOPMENTAL DECISIONS IN ASPERGILLUS-NIDULANS ARE MODULATED BY RAS ACTIVITY

To better understand how Ras controls development of multicellular org anisms, we have chosen Aspergillus nidulans as a model system. When gr own on solid medium, this fungus follows a well-defined program of dev elopment, sequentially giving rise to several cell types which produce three distinct structures: vegetative hyphae, aerial hyphae, and the conidiophore structure. Here we describe a ras homolog found in this f ungus (Aras) and demonstrate that it is an essential gene that regulat es the ordered program of development. We created dominant alleles of this gene and expressed them to different levels in order to vary the ratio of GTP-bound (active) to GDP-bound (inactive) A-Ras protein. Whe n the amount of active Ras is large, nuclear division proceeds, but fu rther development is inhibited at the early step of germ tube formatio n. At an intermediate level of active Ras, aerial hypha formation is i nhibited, while at a low level, conidiophore formation is inhibited. M aintenance of an even lower level of the active Ras is essential for i nitiation and progression of conidiophore formation, the final stage o f development. When the level of active Ras is artificially lowered, e ach stage of development is initiated prematurely except germination, the initial stage of development. Therefore, the progression of the or dered developmental pathway of A. nidulans is dependent upon an initia l high level of active Ras followed by its gradual decrease. We propos e that several concentration thresholds exist, each of which allows de velopment to proceed to a certain point, producing the proper cell typ e while inhibiting further development.