Genetic Analysis 287in vivoby indefinite serial transfers into the abdomen of adult flies. The cultured
discs’ developmental capacity was examined at will by implanting cultured discs
(or parts of the discs) into larvae about to pupate; the disc’s developmental fate
was examined in the emerging adult’s abdomen. As a rule, disc determination was
maintained for many generations — a disc determined to become an eye developed
into an eye after dozens of serial transfers. However, transdetermination to other
developmental fates occurred occasionally, such as an eye disc that developed into
an antenna (see e.g., Gehring and N ̈othiger [1973]). These studies that demon-
strated that the direction of tansdetermination was not random [Kaufman, 1973],
and that it was an epigenetic process involving groups of cells that happened to
be at a specific site at the right time, independent of their previous determination
[Gehring, 1967]. These studies laid the ground for genetic analysis of development,
at the molecular level (see, e.g., Ashburner and Wright [1978]).
When Benzer took up Sturtevant’s idea of genetic-analysis fate mapping of
the Drosophila embryo, locating the foci of behavioral mutants [Hotta and Ben-
zer, 1972] he called the map distancesSturts (sixty years after Sturtevant in-
troduced virtual linear linkage maps, the distances of which were measured in
centi-Morgans). The Sturtevant-Benzer notion was extended further by inducing
genetic changes in larval somatic cells — expressed in the adult as mosaic “spots”
— at different developmental stages of the larvae. This allowed to follow the dy-
namic time scale of the hierarchical differential determination of compartments of
the imaginal discs [Garcia-Bellidoet al., 1979; Garcia-Bellidoet al., 1973]. Specific
selector-genes were identified. These control and regulate differentiation steps and
were found to act on groups of cells (polyclones) that happen to be at the right
place in the right time, irrespective of their genealogical relationship [Crick and
Lawrence, 1975].
One of the serious shortages of genetic analysis of Drosophila was that it con-
centrated almost exclusively on markers of the adult fly for identifying genes. Of
course, there were many lethals who died at embryonic or larval stages of develop-
ment, but hardly any morphological markers were recognized in Drosophila larvae.
This is especially remarkable since so much cytological work was done with the
larval polytenic chromosomes. E. B. Lewis had been studying the structure of
theBithoraxgene complex:bithorax, Ultrabithorax, postbithorax, Contrabithorax,
etc. (see, e.g., the description of the mutants in Lindsley and Grell [1968] by
following the “final”, imaginal morphological patterns of the development [Lewis,
1978]. Eventually, by using new microscopic techniques, he noticed numerous lar-
val markers that have been affected by theBithoraxgenes complex, and extended
his genetic analysis to embryonic and larval stages, to come up with a model of
genetic control of differentiation, based on genes providing an anterior-posterior
gradient in the embryo; the further down the gradient the more genes controlling
differentiation of segmentation were activated [Lewis, 1978]. This model, although
later modified, heralded a new epoch in genetic analysis of development; it pro-
vided a model of differentiation experimentally testable at the molecular level;
it extended the power of genetic analysis to the effective study of early develop-