The histone demethylase KDM5 controls developmental timing inDrosophilaby promoting prothoracic gland endocycles
| Autor: | Michael F. Rogers, Helen M. Belalcazar, Julie Secombe, Coralie Drelon |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
MAPK/ERK pathway Ecdysone Endocycle Embryo Nonmammalian Time Factors MAP Kinase Signaling System Organogenesis Embryonic Development Receptor tyrosine kinase Animals Genetically Modified 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biological Clocks Endocrine Glands Animals Drosophila Proteins Endoreduplication Secretion Lid Molecular Biology KDM5 030304 developmental biology Histone Demethylases 0303 health sciences biology Torso Gene Expression Regulation Developmental Receptor Protein-Tyrosine Kinases MAPK pathway Prothoracic gland Cell biology Drosophila melanogaster Histone chemistry Larva 030220 oncology & carcinogenesis biology.protein Demethylase Drosophila Female Transcription Research Article Developmental Biology |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | In Drosophila, the larval prothoracic gland integrates nutritional status with developmental signals to regulate growth and maturation through the secretion of the steroid hormone ecdysone. While the nutritional signals and cellular pathways that regulate prothoracic gland function are relatively well studied, the transcriptional regulators that orchestrate the activity of this tissue remain less characterized. Here, we show that lysine demethylase 5 (KDM5) is essential for prothoracic gland function. Indeed, restoring kdm5 expression only in the prothoracic gland in an otherwise kdm5 null mutant animal is sufficient to rescue both the larval developmental delay and the pupal lethality caused by loss of KDM5. Our studies show that KDM5 functions by promoting the endoreplication of prothoracic gland cells, a process that increases ploidy and is rate limiting for the expression of ecdysone biosynthetic genes. Molecularly, we show that KDM5 activates the expression of the receptor tyrosine kinase torso, which then promotes polyploidization and growth through activation of the MAPK signaling pathway. Taken together, our studies provide key insights into the biological processes regulated by KDM5 and expand our understanding of the transcriptional regulators that coordinate animal development. Summary: Identification of KDM5 as a new transcriptional regulator of the MAPK signaling cascade provides insights into the molecular mechanisms governing the regulation of ecdysone production and developmental growth control. |
| Databáze: | OpenAIRE |
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