Bhattacharya et al, (Bhattacharya, A., Sudha, S,, Chandra, H, S, and Stewar
d, R, (1999) Development 126, 5485-5493) reported that loss-of-function mut
ations in the flex (female-specific lethal on X) gene caused female-specifi
c lethality because flex(+) acts as a positive regulator of the master swit
ch gene Sex lethal (Sxl), Sri is essential for female development. Key to t
heir conclusion was the ability of flex mutations to suppress the male leth
ality caused by Sxl(M) mutations, which inappropriately activate Sxl female
-specific expression. Here we report our contrary findings that flex mutati
ons fail to suppress even the weakest Sxl(M) alleles, arguing against the p
roposed regulatory relationship between flex and Sri. Instead we show that
the lethal flex phenotype depends on the absence of a Y chromosome, not on
the presence of two X chromosomes. flex lethality is caused by a defect in
the functioning of the X-linked rDNA locus called bobbed, since this defect
is complemented by the corresponding wild-type rDNA complex on the Y.