acting as a DNA-binding transcription regulator, is a 
common factor required for both processes. It may 
act in conjunction with one set of factors (includ- 
ing, for example, sisterless B, a numerator element 
in the X/A ratio) to initiate sex determination of so- 
matic cells and with another set of factors (includ- 
ing, for example, AS-C genes) to initiate neuronal 
precursor formation. In collaboration with Dr. 
David Baltimore (Massachusetts Institute of Tech- 
nology), biochemical evidence has been obtained 
suggesting the da and AS-C products may interact 
directly with each other in regulating transcription 
of downstream genes. 
II. Genes Affecting Neurogenesis. 
One major group of mutations affecting neu- 
rogenesis was previously identified by Dr. Jose 
Campos-Ortega and others. This group includes at 
least seven genes: Notch (N), Delta (Dl), Enhancer 
of split [E(spl)\, almondex (amx), mastermind 
(mam), neuralized (neu), and big brain {bib). De- 
letion of any of these genes leads to hypertrophy of 
both the central and peripheral nervous systems. 
Several genes of this group have already been 
cloned [Dl, E(spl), and A^. The structure of the 
gene products suggests a mode of action through 
cell-cell interaction. Previous genetic and cell trans- 
plantation experiments by Dr. Campos-Ortega and 
his colleagues indicated that those seven genes can 
be divided into several pathways. According to this 
scheme, neu and bib act at steps separate from the 
ones that have already been characterized at the 
molecular level [A^, Dl, E(spl)]. Thus, to obtain a 
more complete understanding of neurogenesis, it is 
desirable to characterize neu and bib at the molec- 
ular level. Dr. Gabrielle Boulianne and Yi Rao have 
cloned neu and bib, respectively. The structure of 
neu suggests that it is a DNA-binding protein. The 
predicted bib product appears to be a membrane 
protein with strong homology to bovine lens major 
intrinsic protein. The products of these genes are 
being studied. 
III. Genes Required in Specifying the Identity of 
Sensory Organ Cells. 
Drosophila embryonic sensory organs can be di- 
vided into three major types according to their 
morphology and possible function: 1) External sen- 
sory organs are situated at the surface of the em- 
bryo and are exposed to the external environment 
(e.g., sensory hairs). These organs probably serve as 
chemoreceptors or mechanoreceptors. 2) The 
chordotonal organ is tube-shaped and is attached 
to the body wall at two ends. These organs proba- 
bly function as stretch receptors. 3) Multiple den- 
drite neurons are characterized by their extensive 
dendritic arborization and are probably touch re- 
ceptors. Dr. Jan and his colleagues are interested in 
finding out how these sensory organ cells acquire 
their identity. 
A. cut. The cut locus is required for external 
sensory organs to acquire their correct identity. 
Embryonic lethal mutations at the cut locus cause 
the transformation of external sensory organs 
into chordotonal organs. More than 200 kilobases 
(kb) from the cut locus have previously been 
cloned by Dr. Joseph Jack. In collaboration with Dr. 
Jack, Dr. Karen Blochlinger and Dr. Bodmer have 
screened for and isolated DNA complementary to 
embryonic mRNA (cDNA) that hybridizes to the 
relevant region of the cut locus. From overlapping 
cDNAs, the sequence of 8,217 base pairs (bp) 
of the cut transcript was determined. The predict- 
ed primary translation product consists of 2,175 
amino acids with an estimated molecular mass of 
240 kDa. The predicted cut protein contains a 
homeodomain. The cut homeodomain appears 
to be the most divergent member of the family 
of homeodomains. Nevertheless, the nine amino 
acids that are invariant in all previously charac- 
terized homeodomains are unaltered in the 
cut homeodomain. Within the predicted cut pro- 
tein there are three internal repeats of 60 amino 
acids, with 55-68% amino acid identity. These 
cut repeats appear to be unrelated to any 
previously determined protein structure. Anti- 
bodies were generated against peptides from the 
predicted sequence to determine where the cut 
gene product is expressed. Immunocytochemistry 
with two of these antisera revealed that the cut 
gene product is expressed in nuclei of cells of ex- 
ternal sensory organs but not in the chordotonal 
organ. This supports the previous conclusion from 
mosaic studies that the cut gene acts autono- 
mously. 
That the cut gene product is a homeodomain- 
containing nuclear protein suggests a specific mode 
of gene function. By analogy to studies of several 
other homeobox-containing genes, the cut gene 
product is expected to act as a DNA-binding pro- 
tein that controls the transcription of certain down- 
stream genes responsible for the actual differentia- 
tion of the external sensory organ. 
Continued 
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