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of early response genes, which mostly encode transcription factors. These
early (or primary) regulatory proteins will then coordinate the expression
of late (or secondary) response genes that ultimately effectuate the required
developmental changes (
Fig. 2.1
B). These downstream effects of steroid and
thyroid hormones are complex events; however, they represent just one side
of the coin. Clearly, we may also ask what happens upstream of the hormone
to understand how the synthesis and release of these hormones are controlled
in the first place. As it turns out, the release of these developmentally impor-
tant hormones is strictly controlled, resulting in precisely timed pulses that
control the onset of developmental transitions such as hatching, molting, and
metamorphosis itself (
Thummel, 1995
).
In this review, we will focus on transcriptional regulators acting down-
stream and upstream of the steroid hormone ecdysone. After a brief historical
perspective, we will review the classic ecdysone hierarchy and its role in
metamorphosis, and then turn our attention to the more recent finding that
many of the transcription factors known to act directly downstream of ec-
dysone also act upstream of the hormone, thus regulating the production of
the hormone itself. In the last part, we will discuss transcription factors that
have not yet been linked to the ecdysone hierarchy but have been shown to
function in the prothoracic gland, the principal source of ecdysone synthesis
in the developing insect.
2. HISTORICAL PERSPECTIVE
The identification of ecdysone as the key molting hormone in the
1950s is a milestone in the history of insect endocrinology. In 1954, Peter
Karlson and colleagues purified 25 mg of ecdysone crystals from 500 kg of
silk moth pupae using the
Calliphora
bioassay to track the activity of the hor-
mone (
Butenandt & Karlson, 1954
). In a series of chemical experiments and
the analysis of the crystals, ecdysone was later shown to be a steroid hormone
(
Huber & Hoppe, 1965; Karlson, Hoffmeister, Hummel, Hocks, &
Spiteller, 1965
). The first evidence that ecdysone has a direct role in regu-
lating gene expression was based on the puffing of the salivary gland polytene
chromosomes. Puffs are enlargements of specific loci on these giant chromo-
somes and were interpreted as local transcriptional activity. In particular, it
was found that some of these puffs were induced rapidly after the addition of
ecdysone to cultured salivary glands of the midge
Chironomus
(
Clever &
Karlson, 1960
). Curiously, some of the puffs were responding rapidly to
the hormone (early puffs), while others were delayed (late puffs). To test
