Proteins produced by the homeotic genes of the Hox family assign diffe
rent identities to cells on the anterior/posterior axis. Relatively li
ttle is known about the signalling pathways that modulate their activi
ties or the factors with which they interact to assign specific segmen
tal identities. To identify genes that might encode such functions, we
performed a screen for second site mutations that reduce the viabilit
y of animals carrying hypomorphic mutant alleles of the Drosophila hom
eotic locus, Deformed. Genes mapping to six complementation groups on
the third chromosome were isolated as modifiers of Deformed function.
Products of two of these genes, sallimus and moira, have been previous
ly proposed as homeotic activators since they suppress the dominant ad
ult phenotype of Polycomb mutants. Mutations in hedgehog, which encode
s secreted signalling proteins, were also isolated as Deformed loss-of
-function enhancers. Hedgehog mutant alleles also suppress the Polycom
b phenotype. Mutations were also isolated in a few genes that interact
with Deformed but not with Polycomb, indicating that the screen ident
ified genes that are not general homeotic activators. True of these ge
nes, cap 'n' collar and defaced, have defects in embryonic head develo
pment that are similar to defects seen in loss of function Deformed mu
tants.