Morphotype switch is a cellular response to external and internal cues. The Cryptococcus neoformans species complex can undergo morphological transitions between the yeast and the filament form, and such morphological changes profoundly affect cryptococcal interaction with various hosts as shown in this research. Filamentation in Cryptococcus was historically considered a mating response activated by pheromone. Recent studies indicate the existence of pheromone-independent signaling pathways but their identity or the effectors remain unknown. Here, we demonstrated that glucosamine stimulated the C. neoformans species complex to undergo self-filamentation independent of the key components of the pheromone pathway. Through a genetic screen we found that Crz1, a transcription factor downstream of the highly conserved phosphatase complex calcineurin, was essential for glucosamine-stimulated filamentation. Glucosamine promoted Crz1 translocation from the cytoplasm to the nucleus. Interestingly, multiple components of the high osmolality glycerol response (HOG) pathway acted as repressors of glucosamine-elicited filamentation through their calcineurin-opposing effect on Crz1s nuclear translocation. The results demonstrate that Cryptococcus can resort to multiple genetic pathways for morphological transition in response to different stimuli. The genetic pathways converge on the transcription factor Znf2 that regulates hyphal differentiation. How Znf2 orchestrates its functions in filamentation remains elusive. In this research, we identified two factors, Brf1 and Snf5, that are essential for Znf2 to fulfill its genetic regulation by a forward genetics screen. As a basidiomycete-specific factor, Brf1 functions in the same genetic pathway as Snf5. Later we found that Brf1 and Sn5 work together in the conserved chromatin remodeling complex called SWI/SNF. The SWI/SNF complex is required to open up the chromatin of promoter regions of Znf2 and its targets. Meanwhile, as a subunit in the SWI/SNF complex, Brf1 is required for transcription factor Znf2s full association to DNA. This molecular and genetic study has advanced our understanding in the regulations of hyphal cellular differentiation in Cryptococcus, yielded novel insights on the conserved and species-specific regulation mechanisms in other fungi, and raised possibilities for diminishing Cryptococcus virulence by inducing hyphal growth in the host.