In Drosophila, glial cell development depends on the gene glial cells missi
ng (gcm), gem activates the expression of other transcription factors such
as POINTED and REPO, which control subsequent glial differentiation. In ord
er to better understand glial cell differentiation, we have screened for ge
nes whose expression in glial cells depends on the activity of POINTED. Usi
ng an enhancer trap approach, we have identified loco as such a gene. loco
is expressed in most lateral CNS glial cells throughout development. Embryo
s lacking loco function have an normal overall morphology, but fail to hatc
h. Ultrastructural analysis of homozygous mutant loco embryos reveals a sev
ere glial cell differentiation defect. Mutant glial cells fail to properly
ensheath longitudinal axon tracts and do not form the normal glial-glial ce
ll contacts, resulting in a disruption of the blood-brain barrier. Hypomorp
hic loco alleles were isolated following an EMS mutagenesis. Rare escapers
eclose which show impaired locomotor capabilities, loco encodes the first t
wo known Drosophila members of the family of Regulators of G-protein signal
ling (RGS) proteins, known to interact with the a subunits of G-proteins, L
OCO specifically interacts with the Drosophila G alpha i-subunit. Strikingl
y, the interaction is not confined to the RGS domain. This interaction and
the coexpression of LOGO and G alpha i suggests a function of G-protein sig
nalling for glial cell development.