Genetic Control of Morphogenesis in Drosophila 
Philip A. Beachy, Ph.D. — Assistant Investigator 
Dr. Beachy is also Assistant Professor in the Department of Molecular Biology and Genetics at the Johns 
Hopkins University School of Medicine. He did his graduate work in the Department of Biochemistry at 
Stanford University School of Medicine with David Hogness. Before joining the Hughes Institute at Johns 
Hopkins, he spent two years as Staff Associate at the Carnegie Institution's Department of Embryology. 
He has been the recipient of several fellowships, including a Sloan Foundation Fellowship in Neuroscience. 
TWO conceptually distinct processes operate 
during Drosophila embryogenesis. In the 
first of these, a detailed system of spatial informa- 
tion is generated by a cascade of interactions 
among several groups of genes and their prod- 
ucts. During morphogenesis, the second phase, 
interpretation of the blueprint results in the com- 
plex arrangement of structures seen in the larva 
and adult. 
The first process is initiated during oogenesis 
by maternal input of broad spatial cues. The in- 
teracting genes that receive and refine this infor- 
mation in the embryo have been extensively 
characterized, in most cases at the molecular 
level. Much less is known about how morphogen- 
esis is directed, though it is generally believed to 
occur through regulation of target genes by the 
localized proteins generated during construction 
of the blueprint. This laboratory's current inter- 
ests center upon two groups of genes that operate 
at the interface between these processes, the seg- 
ment polarity genes and the homeotic genes. 
The hedgehog Segment Polarity Gene 
The segment polarity group is the latest acting 
of the segmentation gene groups. It functions in 
the refinement of positional information at the 
level of individual cells within embryonic seg- 
ments. During the earlier, syncytial period of Dro- 
sophila embryogenesis, the absence of cell mem- 
branes permits diff'usion between nuclei, which 
can account for many of the interactions between 
early acting segmentation genes and their prod- 
ucts. Some segment polarity genes, however, are 
expressed and function long beyond the syncytial 
stages. Communication between cells for refine- 
ment of positional information requires signaling 
across cell membranes. Consistent with a role in 
signaling, the products of many segment polarity 
genes are secreted or localized to nonnuclear 
compartments. 
During the past year our laboratory isolated and 
characterized the segment polarity gene hedge- 
hog. The hedgehog locus was identified in the 
exhaustive genetic screens carried out by Chris- 
tiane Niisslein-Volhard, Eric Wieschaus, and their 
colleagues, and was named for the bristle pattern 
observed in mutant larvae. The phenotype resem- 
bles that of a number of other segment polarity 
genes, including wingless. 
The wingless gene is expressed within each 
segment in a stripe of cells adjacent to that in 
which engrailed, another segment polarity gene, 
is expressed. The normal function of each gene is 
required within its own stripe for maintenance of 
the other gene's expression within the neighbor- 
ing (but not overlapping) stripe. The mutual re- 
quirement of each gene for the other's continued 
expression in a neighboring cell implies a mecha- 
nism for communication between these cells. 
Since wingless encodes a secreted peptide factor 
and engrailed a homeodomain-containing tran- 
scription factor, additional components must be 
involved in the signaling mechanism. 
Interest in this pathway has been stimulated by 
recent results elsewhere indicating that targeted 
inactivation of the murine homologues of wing- 
less and engrailed produce specific developmen- 
tal defects of the midbrain and cerebellum. Other 
genes that may be involved in this pathway are 
hedgehog and patched, which from genetic evi- 
dence appear to interact. While patched encodes 
a protein with apparent multiple membrane- 
spanning domains, the product of the hedgehog 
gene had not previously been characterized. We 
gained entry into the hedgehog locus with the aid 
of an "enhancer trap" P-transposable element in- 
serted near the gene. Analysis revealed a se- 
quence capable of encoding a protein of 471 
amino acid residues. This includes a region near 
the amino terminus suggestive of targeting to the 
secretory pathway, either as a secreted polypep- 
tide or as an integral membrane protein. 
Either possibility would permit interaction of 
the hedgehog protein with the membrane-span- 
ning patched protein, in accordance with the ge- 
netic prediction. Also consistent with such an in- 
teraction, the hedgehog gene is expressed 
coincidently with engrailed, while patched is 
expressed coincidently with wingless in adjacent 
cells. The physical nature of the interaction re- 
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