Our long-term goal is to understand how ecdysteroids and juvenile hormone (JH) act to coordinate insect growth and development. Ecdysteroids cause molting, both suppressing on-going intermolt gene expression and activating the cascade of genes necessary for the molt. Moreover, ecdysteroids are important for maintenance of tissue synchrony during the molt. JH determines whether the molt will be progressive or not; in its presence metamorphosis cannot occur. Thus, JH prevents ecdysteroid's activation of previously unexpressed genes that allow the cell to change its differentiated state. Our model for studying this action is the insect epidermis which makes the cuticle, i.e. the exoskeleton, and which is a single cell layer thick and can readily be cultured.
Our specific aims for the next 5 years are: 1) To characterize the regulatory regions of the several larval cuticular genes and dopa decarboxylase and to study their possible interactions with ecdysteroid and JH receptors and/or the transcription factors that these hormones induce. 2) To clone, characterize, and study the hormonal control of a pupal-specific cuticle gene to complete our arsenal of epidermal genes that are hormonally regulated at metamorphosis. 3) To determine the role in molting and metamorphosis of the ecdysteroid-induced transcription factor (""""""""RAR"""""""") that shows significant similarity to the mammalian retinoic acid receptor. 4) To examine possible changes in EcR subtypes in the epidermis through larval molting and metamorphosis by in situ hybridization and immunocytochemistry and how they are regulated by the hormonal milieu. These studies will allow us to define at the molecular level how ecdysteroids and JH regulate insect growth, molting, and metamorphosis. This information can lead to design of new types of insect growth regulators essential to the control of disease vectors. Also, emerging similarities between the actions of JH and of retinoic acid in the regulation of cell differentiation, particularly in mammalian epidermis, make the insect epidermis a possible nonvertebrate model for study of common mechanisms involved.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
8R01GM060122-24
Application #
2855915
Study Section
Special Emphasis Panel (ZRG5-TMP (01))
Project Start
1979-01-01
Project End
2001-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
24
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Washington
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Suzuki, Yuichiro; Koyama, Takashi; Hiruma, Kiyoshi et al. (2013) A molt timer is involved in the metamorphic molt in Manduca sexta larvae. Proc Natl Acad Sci U S A 110:12518-25
Mirth, Christen K; Truman, James W; Riddiford, Lynn M (2009) The ecdysone receptor controls the post-critical weight switch to nutrition-independent differentiation in Drosophila wing imaginal discs. Development 136:2345-53
Zhou, Baohua; Williams, Darren W; Altman, Janet et al. (2009) Temporal patterns of broad isoform expression during the development of neuronal lineages in Drosophila. Neural Dev 4:39
Suzuki, Yuichiro; Squires, Diego C; Riddiford, Lynn M (2009) Larval leg integrity is maintained by Distal-less and is required for proper timing of metamorphosis in the flour beetle, Tribolium castaneum. Dev Biol 326:60-7
Erezyilmaz, Deniz F; Kelstrup, Hans C; Riddiford, Lynn M (2009) The nuclear receptor E75A has a novel pair-rule-like function in patterning the milkweed bug, Oncopeltus fasciatus. Dev Biol 334:300-10
Erezyilmaz, Deniz F; Rynerson, Melody R; Truman, James W et al. (2009) The role of the pupal determinant broad during embryonic development of a direct-developing insect. Dev Genes Evol 219:535-44
Zartman, Jeremiah J; Yakoby, Nir; Bristow, Christopher A et al. (2008) Cad74A is regulated by BR and is required for robust dorsal appendage formation in Drosophila oogenesis. Dev Biol 322:289-301
Minakuchi, Chieka; Zhou, Xiaofeng; Riddiford, Lynn M (2008) Kruppel homolog 1 (Kr-h1) mediates juvenile hormone action during metamorphosis of Drosophila melanogaster. Mech Dev 125:91-105
Suzuki, Yuichiro; Truman, James W; Riddiford, Lynn M (2008) The role of Broad in the development of Tribolium castaneum: implications for the evolution of the holometabolous insect pupa. Development 135:569-77
Zhou, Xiaofeng; Riddiford, Lynn M (2008) rosy Function is required for juvenile hormone effects in Drosophila melanogaster. Genetics 178:273-81

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