What Goes Up Must Come Down: Transcription Factors Have Their Say in Making Ecdysone Pulses - Current Topics in Developmental Biology - page 43

embryogenesis, b FTZ-F1 is also expressed in the early stages of puparium
formation ( Yamada et al., 2000; Yu et al., 1997 ). Mutations in b ftz-f1
severely perturb the ecdysone signaling pathway at the onset of metamor-
phosis and consequently result in prepupal lethality. Later, it was shown that
b ftz-f1 functions as a competence factor during prepupal development, en-
suring that the responses to the late larval ecdysone pulse are different from
the prepupal pulse 12 h later ( Broadus, McCabe, Endrizzi, Thummel, &
Woodard, 1999 )( Fig. 2.1 B). Taken together, the interplay between nuclear
receptors E75, DHR3, and DHR4 controls the expression of b ftz-f1 during
the prepupal stage, thereby safeguarding the appropriate sequence of pro-
grams necessary for the progression of pupal development.
6. UPSTREAM OF THE HORMONE: ECDYSONE
SYNTHESIS IN THE PROTHORACIC GLANDS
It is well established that the prothoracic glands are the principal source
of ecdysone during larval development ( Fig. 2.2 A). In total, six major ecdy-
sone pulses control embryogenesis, the molts, the onset of metamorphosis,
and the differentiation of adult tissues. In addition, three minor pulses of ec-
dysone that occur in the third larval instar are critical for physiological and
behavioral changes prior to metamorphosis, including the commitment of
a larva to a pupal fate (critical weight checkpoint), the induction of the glue
genes that allow the pupa to attach to a solid substrate, and the transition from
feeding to wandering behavior ( Davidowitz, D'Amico, & Nijhout, 2003;
Lehmann, 1996; Mirth, Truman, & Riddiford, 2005; Riddiford, 1993;
Sokolowski, 2001; Warren et al., 2006 )( Fig. 2.2 B). While these ecdysone
pulses are well defined, it remains rather unclear as to how the onset, ampli-
tude, and duration of these hormone peaks are regulated. Our current under-
standing is based on two cornerstones: The PTTH (prothoracicotropic
hormone) signaling pathway and the enzymes involved in ecdysone biosyn-
thesis. PTTH is a brain-derived peptide that is rhythmically released from two
pairs of neurons and acts as a temporal stimulus for ecdysone production
( Fig. 2.4 A). Ultimately, PTTH must impinge on ecdysone biosynthesis for
which currently eight enzymes and their corresponding genes have been iden-
tified; however, how this is accomplished is largely unclear. In this section, we
will summarize our current understanding of the PTTH signaling pathway,
and how it might regulate ecdysone biosynthesis.
The prothoracic gland has to import and transport dietary cholesterol,
which serves as a precursor for the synthesis of ecdysone ( Gilbert, 2004;