Haploid yeast invades solid agar in response to nutrient limitation. To dec
ipher the cues that underlie invasion, we have developed a single cell inva
sive growth assay. Using this assay, as well as the traditional plate-washi
ng assay, we show that invasive growth occurs in response to glucose deplet
ion. in the absence of glucose (or other fermentable sugar), individual cel
ls adopted a nonaxial budding pattern and elongated morphology within the f
irst cell divisions, and invasion into the agar was observed in microcoloni
es containing as few as 10 cells. In support of this observation, we found
that glucose suppressed the hyperinvasive growth morphology of STE11-4 pbs2
. hsl7, and RAS2V19 mutations. In addition, removal of glucose from YPD med
ium caused constitutive invasion in wild-type cells. We tested glucose cont
rol proteins for a role in invasion and found that Snf1, a protein required
for derepression of glucose-repressed genes, was required for invasive gro
wth. The transcription factor Sip4 which interacts with Snf1 and is induced
during the diauxic shift, had an inhibitory role on invasive growth, sugge
sting that multiple mechanisms are required for glucose depletion-dependent
invasion.