precursors may involve the actions of certain neuro- 
nal precursor genes, which lock a cell into a particu- 
lar fate. The identity of a neuronal precursor is fur- 
ther specified by the neuronal-type selector gene. 
Proneural Genes 
The proneural genes define a state that makes 
cells competent to become neuronal precursors. 
The prototype of proneural genes are the genes of 
the achaete-scute complex {AS-C). Recent studies 
from the groups of Drs. Juan Modolell, Alain Ghy- 
sen, and Sean Carroll (HHMI, University of Wiscon- 
sin) provide strong support for the notion of pro- 
neural genes. 
Previous studies indicate that there should be 
other proneural genes in addition to AS-C. The Dro- 
sophila sensory nervous system consists of three ma- 
jor types of sensory organs: 1) the es (external sen- 
sory) organ, 2) the ch (chordotonal) organ, and 3) 
the md (multiple dendrite) neuron. All the es or- 
gans and the majority of md neurons require AS-C 
for formation, whereas ch organ formation is inde- 
pendent of AS-C. Presumably there is an additional 
proneuronal gene required for ch organ formation. 
Drs. Yves Grau and Andy Jarman found this missing 
proneural gene, atonal, based on the fact that all 
known proneural genes contain a basic helix-loop- 
helix (bHLH) motif. They lined up all the known 
bHLH sequences, designed primers for polymerase 
chain reactions, and managed to clone atonal, 
atonal has the predicted properties: 1) its expres- 
sion pattern prefigures the location of ch organs, 2) 
deletion of the chromosomal region containing 
atonal results in a failure of ch organ formation, and 
3) ectopic expression of atonal leads to formation 
of ectopic ch organs. 
Neurogenic Genes 
Previous studies from the laboratory of Dr. Jose 
Campos-Ortega have shown that removing the func- 
tion of any of the six known zygotic neurogenic 
genes — Notch (N), Delta (Dl), the Enhancer of 
split complex [E(spl)C\, mastermind {mam), 
neuralized (neu), and big brain {bib) — leads to 
hypertrophy of both the central and peripheral ner- 
vous systems, presumably as a result of losing lateral 
inhibition. These six neurogenic genes can be 
placed into two separate genetic pathways. A'^and Dl 
belong to one pathway. Work from the laboratories 
of Drs. Spyridon Artavanis-Tsakonis (HHMI, Yale 
University) and Michael Young (HHMI, Rockefeller 
University) strongly suggests that the protein prod- 
ucts of N and Dl mediate a receptor-ligand interac- 
tion between neighboring cells, bib also encodes a 
membrane protein, like A'^and Dl, but belongs to a 
separate genetic pathway. Phenotype analysis re- 
vealed that bib mutants are qualitatively different 
from A'^and DlnuW mutants. In A^and Z)/ mutants, all 
cells in the proneural clusters develop into neuro- 
nal precursors, whereas in bib mutants only a subset 
of cells do so. This suggests that cells in proneural 
clusters are not completely equivalent. The se- 
quence of bib shows considerable similarity with 
certain transporter molecules, suggesting that bib 
may also function in controlling such transport. 
Neurogenic genes were named as such because 
they were originally identified by their function in 
neural development. However, recent studies re- 
vealed that they have a much broader function. Dr. 
Young's laboratory found that neurogenic genes are 
involved in specifying muscle cell fate. Dr. Hannele 
Ruohola-Baker in Dr. Jan's laboratory found that 
neurogenic genes also control follicle cell fates dur- 
ing oogenesis. Thus neurogenic genes as a group are 
involved in selecting a subset of cells among a group 
of equivalent, pluripotent cells to take on a specific 
fate. These neurogenic genes may be considered as a 
functional cassette that mediates cell interaction in 
various developmental contexts, including neuro- 
genesis, oogenesis, and muscle development. 
Neuronal Precursor Genes 
Once a cell is singled out to become a neuronal 
precursor, it develops differently from its neigh- 
bors. Dr. Jan's laboratory identified several neuronal 
precursor genes (including prospero and deadpan) 
that are expressed in neuronal precursors but not 
their surrounding ectodermal cells. They proposed 
that neuronal precursor genes have important roles 
in directing neuronal precursor differentiation; 
each gene may control a subset of neuronal proper- 
ties. Consistent with this hypothesis, it has been 
found that prospero appears to control aspects of 
axonal outgrowth. 
Analysis of the neuronal precursor gene deadpan 
provided an unexpected dividend. It is known from 
the work of Dr. Calvin Bridges that sex in Drosoph- 
ila is determined by the X chromosome to autosome 
ratio (X/A ratio). Previous studies by Dr. Tom Cline 
demonstrated that sex lethal (Sxt) is the master reg- 
ulatory gene of Drosophila sex determination. In 
male (X/A = 0.5) Sxl is off, and in female (X/A = 1) 
Sxl is on. There are numerator genes that count the 
X chromosome . It was not known whether a denomi- 
nator gene(s) that counts the autosomes also exists. 
Susan Younger-Shepherd in Dr. Jan's laboratory 
found that deadpan is in fact a denominator gene. 
An interesting link between Drosophila neural de- 
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