genomic modifications during development and in 
their functional significance. 
Dpll87 and the Y Chromosomes: 
Genomic Changes During Development 
Dr. Spradling's studies have primarily utilized 
Dpi 187, the smallest known functional chromo- 
some in any multicellular eukaryote. A 1 50- to 220- 
kb block (1 kb = 1,000 DNA base pairs) of Dpi 187 
"euchromatin" encodes nine genes, while the re- 
maining 1,100 kb is classed as heterochromatin, a 
little-understood but common component of eukary- 
otic genomes frequently associated with centro- 
meres and telomeres. Heterochromatic regions are 
folded differently than euchromatic ones, consist 
mostly of repeated DNA sequences and transposons, 
and undergo copy number changes during Drosoph- 
ila development. 
The Drosophila Y chromosome provides a second 
system for these studies. It encodes a nucleolus and 
only six genes, despite being 40 times larger than 
Dpi 187. The only functional requirement for these 
genes is during spermatogenesis, and Y-linked se- 
quences are virtually lost in many other differen- 
tiated cells during development. 
The most dramatic changes detected so far are in 
the size of Dp 11 87 molecules. The chromosome 
migrated on pulsed-field gel electrophoresis of DNA 
from embryos as 1 ,300 kb in length, but in the ovary 
two new bands of only 680 kb and 400 kb were 
observed. These altered molecules derived from the 
two major ovarian cell types, the nurse and follicle 
cells. Smaller, more heterogeneous Dpi 187 mol- 
ecules were also found in these cells with a fre- 
quency that correlated with the variegated expres- 
sion of a marker gene on the chromosome. Dr. 
Spradling and his colleagues interpreted these ob- 
servations as supporting their previous proposal 
that a DNA-elimination-like process occurs during 
the normal development of Drosophila nurse and/ 
or follicle cells. (These studies were also supported 
by a grant from the National Institutes of Health.) 
Genetic Regulation of Oogenesis 
Dr. Spradling's group has continued to study sev- 
eral aspects of Drosophila oogenesis that may be 
related to the changes described above. The cells 
that will contribute to each new egg derive from 
both germline and somatic stem cells. The number, 
location, and stem cell character of these cells are 
being investigated. Laser ablation studies verified 
the presence of a small number of germline stem 
cells in the anterior part of each ovariole. Three dif- 
ferent groups of somatic cells were identified that 
adjoin these cells as candidate regulators of their 
function. Three genes, l)Yb, ovarette, and piwi, 
have been identified and cloned that appear to be 
required for normal germline stem cell function. 
Mutations in any one of these genes caused all the 
germline cells in the ovary to differentiate. One of 
the genes, piwi, has a similar effect on male germ- 
line stem cells in the testis. 
Several later steps in oogenesis are also being stud- 
ied. Nurse cells produce large amounts of ribosomes 
within an unusually large nucleolus and transport 
them to the oocyte. Several genes have been identi- 
fied in which nurse cells fail to function properly 
and degenerate. The possible role of juvenile hor- 
mone in regulating egg development has also been 
addressed by isolating several new genes that block 
development near the onset of yolk uptake, a check- 
point thought to be controlled by this hormone. 
Drosophila Genome Resource 
Large-scale genetic screens for mutations induced 
by single P elements have proven of great value over 
the past five years. A collection of 1,800 single P- 
element-induced lethal mutations generated here 
and in the laboratories of Drs. Gerald Rubin (HHMI, 
University of California, Berkeley), Matthew Scott 
(Stanford University), and Lily and Yuh Nung Jan 
(HHMI, University of California, San Francisco) 
have recently been incorporated into a genome proj- 
ect designed to facilitate molecular and genetic stud- 
ies of Drosophila. In collaboration with Dr. Rubin, 
localization and complementation studies will 
whittle the collection to ~ 1,1 00 strains, each of 
which defines a different vital locus. Sequences 
flanking each insertion site will be physically 
mapped by collaborators at Lawrence Berkeley Labo- 
ratories (Michael Palazzolo and Christopher Martin) 
and at Harvard (Dr. Daniel HartI) with support from 
the National Center for Human Genome Research, 
National Institutes of Health. Information devel- 
oped by the project will be distributed on-line, and 
both clones and insertion strains will be furnished to 
the research community. 
Dr. Spradling is also Staff Member in the Depart- 
ment of Embryology at the Carnegie Institution of 
Washington, Baltimore; Adjunct Professor of Biol- 
ogy at the fohns Hopkins University; and Adjunct 
Professor of Molecular Biology and Genetics at the 
Johns Hopkins University School of Medicine. 
Books and Chapters of Books 
Spradling, A.C. 1992. Developmental genetics of 
oogenesis. In Drosophila Development (Bate, M., 
and Martinez-Arias, A., Eds.). Cold Spring Harbor, 
NY: Cold Spring Harbor, pp 1-69. 
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