Insights into the molecular basis of the hormonal control of molting and metamorphosis from Manduca sexta and Drosophila melanogaster

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Abstract

This short review summarizes our current knowledge about the role of transcription factors regulated by ecdysteroids and juvenile hormone (JH) in larval molting and metamorphosis in the tobacco hornworm, Manduca sexta, and Drosophila melanogaster. We show new evidence that EcR-A/USP-2 and E75A contribute to the down-regulation of MHR3 after the peak of ecdysteroid. Also, there is suggestive evidence that both MHR4 and βFTZ-F1 may regulate the expression of dopa decarboxylase as the ecdysteroid titer declines. We summarize the regulation by JH of the Broad transcription factor that normally appears in the epidermis in the final larval instar and specifies pupal cuticle formation at the metamorphic molt. Premature expression of different Broad isoforms also is shown to cause precocious degeneration of the prothoracic glands as well as to prevent ecdysteroid release during its presence.

Introduction

Insect molting and metamorphosis are governed by the ecdysteroids and juvenile hormone (JH) with ecdysone (E) and 20-hydroxyecdysone (20E) orchestrating the molting process and JH determining the nature of the molt. JH is normally present during larval life to allow growth of the larva and the progression from one larval stage to the next until the larva attains a proper size for metamorphosis. The neurosecretory hormone prothoracicotropic hormone (PTTH) directs the precise timing of the molt since its release is governed by both intrinsic factors such as size and extrinsic factors, such as photoperiod and temperature. The existence and basic function of each of these hormones were discovered by the pioneers of insect endocrinology: PTTH by Kopec (1922), ecdysone by Fraenkel (1935), and juvenile hormone (JH) by Wigglesworth (1934). The hormones were then isolated and their chemical structure elucidated [E by Karlson et al. (1965) and Huber and Hoppe (1965); 20E by Hampshire and Horn, 1966, Hocks and Weichert, 1966; and Hoffmeister and Grutzmacher (1966); JH by Williams (1956) and Röller et al., (1967); and finally PTTH by Kawakami et al. (1990) and Kataoka et al. (1991)]. Yet there was still much to do to determine the action of these hormones, and Larry Gilbert has been a prime mover in this area of insect endocrinology over the past 45 years.

I first met Larry Gilbert when I went to his PhD thesis defense at Cornell University in 1958 during my visit there for a veterinary school interview and for possible graduate study in Zoology. Part of his work was on the presence of juvenile hormone (JH) in a variety of organisms and tissues, both vertebrate and invertebrate, and most particularly in the adrenal cortex (Gilbert and Schneiderman, 1958a, Gilbert and Schneiderman, 1958b). I was interested since I had just finished my undergraduate honors thesis at Radcliffe College on JH in various mammalian organs and had also found JH-like activity in extracts from the adrenal cortex (Williams et al., 1959). At that time unbeknownst to me, Howard Schneiderman and Carroll Williams were major competitors in the study of JH action, which led to Professor Schneiderman’s comment that I was “a spy from Harvard” upon my introduction to him and Larry after the talk. Much later when I returned to insect endocrinology and began working on the tobacco hornworm, Manduca sexta, Larry became a staunch supporter of my work as we did complementary studies to make the tobacco hornworm, Manduca sexta, the “laboratory rat” of insect endocrinology. I much value these interactions over the years.

The following is a review of recent studies in my laboratory using both Manduca and Drosophila to study the action of these three hormones, concentrating primarily on the ecdysteroids and JH. Importantly, the ease of biochemical and endocrinological manipulations in Manduca coupled with the ease of genetic and molecular manipulation in Drosophila have allowed us to begin to unravel the mystery of the control of insect molting and metamorphosis. Although the molecular action of the ecdysteroids is quite well understood (Henrich et al., 1999, Riddiford et al., 2001, Thummel and Chory, 2002), we still, however, do not fully understand how JH acts at the molecular level (Gilbert et al., 2000).

The role of JH during postembryonic insect development is to direct the action of ecdysone and 20E, its presence preventing these two hormones from causing a switch in differentiative program from larval to pupal or from pupal to adult (Riddiford, 1994, Riddiford, 1996). The ecdysteroid-coordinated molting process is unaffected by the presence or absence of JH. At metamorphosis JH disappears, then ecdysone and 20E appear in low amounts and, in the absence of JH, pupally commit the epidermis to pupal differentiation when it next sees a molting surge of ecdysteroid (Riddiford, 1978). Therefore, we have sought to study the action of JH on the molecular level by looking at its regulation of ecdysteroid-regulated transcription factors in the abdominal epidermis during both a larval molt and at metamorphosis.

Section snippets

The ecdysteroid-regulated cascade of transcription factors during the final larval molt of Manduca

In Manduca epidermis, a number of transcription factors in the nuclear receptor superfamily appear and disappear during the last larval molt and are regulated by the ecdysteroid titer (Riddiford et al., 1999; Fig. 1). When the ecdysteroid titer begins to increase, mRNAs for both the B1 isoform of the ecdysone receptor (EcR-B1) (Jindra et al., 1996, Hiruma et al., 1999) and E75A [an “early” ecdysone-induced transcription factor in Drosophila (Segraves and Hogness, 1990, Bialecki et al., 2002)] (

Role of JH in the prevention of metamorphosis

In the final larval instar, the JH titer declines and a low amount of ecdysteroid (1:1 ecdysone:20E; Bollenbacher et al., 1981) in the absence of JH initiates metamorphosis. In a polymorphic tissue such as the abdominal epidermis of Manduca, this initiation means the switching of the program of differentiation from larval to pupal (Riddiford, 1976, Riddiford, 1978). This switch involves the turning-off of many larval-specific cuticle genes and the unmasking of previously unexpressed pupal

Acknowledgements

We thank Professor James Truman for the images in Fig. 5, Fig. 7 and for comments on the manuscript. The unpublished work was supported by grants from NSF (IBN 9817339), NIH (GM 60122) and USDA (2001-35302-10918).

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