suggesting that the tyrosine kinase encoded by itk 
functions in a signal transduction pathway unique to 
T lymphocytes. RNAs for itk and for the a chain of 
the IL-2 receptor are co-induced by the T cell mito- 
gen IL-2. By 2 hours after IL-2 administration, the 
steady-state level of itk RNA increased eightfold, im- 
plicating itk in the response of T cells to this lym- 
phokine. 
Dr. Desiderio is also Associate Professor of Mo- 
lecular Biology and Genetics at the Johns Hopkins 
University School of Medicine. 
Articles 
Desiderio, S.V. 1992. B-cell activation. Curr Opin 
Immunol 4:252-256. 
Dymecki, S.M., ZwoUo, P., Zeller, K., Kuhajda, 
F.P., and Desiderio, S.V. 1992. Structure and de- 
velopmental regulation of the B-lymphoid tyro- 
sine kinase gene blk. J Biol Chem 267:4815- 
4823. 
Garcia, K.C., Desiderio, S.V., Ronco, P.M., Ver- 
roust, P.J., and Amzel, L.M. 1992. Recognition of 
angiotensin II: antibodies at different levels of an 
idiotypic netw^ork are superimposable. Science 
257:528-531. 
Wilson, R.B., Kiledjian, M., Shen, C P., Benezra, R., 
Zwollo, P., Dymecki, S.M., Desiderio S.V., and 
Kadesch, T. 1991. Repression of immunoglobu- 
lin enhancers by the helix-loop-helix protein Id: 
implications for B-lymphoid-cell development. 
Mol Cell Biol 11:6185-6191. 
TRANSCRIPTION CONTROL DURING EARLY DROSOPHILA DEVELOPMENT 
Claude Desplan, Ph.D., Associate Investigator 
The goal of Dr. Desplan's laboratory is to under- 
stand the molecular mechanisms involved in the reg- 
ulatory interactions among developmental genes. In 
light of the complexity of the system, a productive 
approach is, first, to characterize the molecular in- 
teractions in vitro and, second, to design in vivo 
systems to test models of regulatory interactions 
consistent v^ith properties uncovered through the 
first step. Dr. Desplan and his colleagues are investi- 
gating the events leading to patterning in two major 
systems in the Drosophila embryo. One involves the 
establishment of the early anterior pattern, while 
the other is a structure-function analysis of genes 
that control later steps of development. 
Dimerization and DNA-binding Specificity 
of the Homeodomain 
Most developmental processes involve genes that 
encode a homeodomain (HD). The HD includes a 
domain similar to the helix-turn-helix motif present 
in many prokaryotic DNA-binding transcriptional 
regulators. The analyses by Dr. Desplan and his col- 
leagues of the HD in vitro and in cell culture have 
led them to propose that the specificity changes 
among classes of HDs are due to the nature of a sin- 
gle amino acid at position 9 of the recognition helix. 
A powerful selection procedure from a library of 
random sequences has led to the discovery that at 
least some HDs are able to dimerize cooperatively 
on palindromic sites of DNA. 
The geometry of this dimerization, which is sur- 
prising in view of the published structures of HDs, is 
regulated by residue 9 of the recognition helix. 
Changing this position can change not only the base 
pairs recognized by the HD but also the spacing re- 
quirement between the two halves of the palin- 
drome. Also, when residue 9 is a lysine, as in Bicoid, 
the HD binds with high specificity as a monomer 
and does not appear capable of cooperative dimer- 
ization. These observations are important, because 
they suggest that various HDs form heterodimers, a 
process that may help explain some of the combina- 
torial interactions observed between segmentation 
genes. 
The paired Gene Encodes a Multifunctional 
Transcription Factor 
In addition to an HD, the product of the paired 
gene, Prd, contains domains that are conserved in 
other developmental gene products. The Paired do- 
main also mediates DNA binding, making Prd a bi- 
functional transcription factor. Although both the 
Paired domain and the HD can bind to DNA indepen- 
dently, they can also bind cooperatively to adjacent 
sites when both are present in the same molecule. 
The cooperation between the two motifs may re- 
fine the functional specificity of genes contain- 
ing highly related domains. An in vivo structure- 
function analysis of the product of prd is an 
attempt to correlate the multiple DNA-binding func- 
tions of Prd defined in vitro with the multiple ge- 
netic functions of the prd gene, as a regulator of 
GENETICS 181 
