Growth Control


Steroids positively regulate organ growth

Animals have a determined species-specific body size that results from the combined action of hormones and signaling pathways regulating growth rate and duration. In Drosophila, the steroid hormone ecdysone controls developmental transitions, thereby regulating the duration of the growth period. We have shown that ecdysone promotes the growth of imaginal discs in mid-third instar larvae, since imaginal discs from larvae with reduced or no ecdysone synthesis are smaller than wild type due to smaller and fewer cells. Insulin-like peptides are produced and secreted normally in larvae with reduced ecdysone synthesis, and upstream components of insulin/insulin-like signaling are activated in their discs. Instead, ecdysone appears to regulate the growth of imaginal discs via Thor/4E-BP, a negative growth regulator downstream of the insulin/insulin-like growth factor/Tor pathways. Discs from larvae with reduced ecdysone synthesis have elevated levels of Thor, while mutations in Thor partially rescue their growth. The regulation of organ growth by ecdysone is evolutionarily conserved in hemimetabolous insects, as shown by our results obtained using Blattella germanica. Our data provided new insights into the relationship between components of the insulin/insulin-like/Tor and ecdysone pathways in the control of organ growth.








Proliferation is reduced in imaginal discs exposed to low ecdysone levels.  (A-D) Single plane confocal pictures of wing discs stained for anti-pH3, taken under the same conditions.

Adapted from: Herboso et al. Ecdysone promotes growth of imaginal discs through the regulation of Thor in D. melanogaster. Sci Rep. 2015 Jul 22;5:12383. doi: 10.1038/srep12383. PMID:

26198204











Steroids synthesis and growth depend on SUMOylation and Ftz-f1

Post-translational modifications by the Small-Ubiquitin MOdifier SUMO, are necessary for the synthesis of steroids. When SUMO is reduced in the steroid gland, the animals are not able to continue development and grow to abnormal size. The transcription factor Ftz-f1, homologous to the mammalian nuclear receptor Steroidogenic Factor 1 SF1, is crucial in steroidogenesis by the regulation of the Scavenger Receptors, involved in cholesterol capture.







Larvae with low SUMO (smt3i) do not pupariate but continue growing as larvae, getting approximately double weight at 18-21 days.

Adapted from: Talamillo et al. Smt3 is required for Drosophila melanogaster metamorphosis.

Development. 2008 May;135(9):1659-68. doi: 10.1242/dev.020685. PMID: 18367553










 

Publications on Growth Control

Other Laboratory Publications



Scientific Reports (2015) 5: 12383. doi:10.1038/srep12383.

The steroid hormone ecdysone promotes imaginal discs growth in Drosophila melanogaster.

Herboso L, Oliveira MM Talamillo A, Pérez C, González M, Martin D, Sutherland JD, Shingleton AW, Mirth C and Barrio R.*

PMID: 26198204



PLoS Genetics 2013, 9(4): e1003473. doi:10.1371/journal.pgen.1003473 (2013)

Scavenger Receptors Mediate the Role of SUMO and Ftz-f1 in Drosophila Steroidogenesis.

Talamillo A, Herboso L, Pirone L, Pérez C, González M, Sánchez J, Mayor U, Lopitz-Otsoa F, Rodriguez MS, Sutherland JD and Barrio R.

PMID: 23637637





Biochem J. 2011 Sep 15;438(3):437-45.

Drosophila Sal and Salr are transcriptional repressors.

Sánchez J, Talamillo A, González M, Sánchez-Pulido L, Jiménez S, Pirone L, Sutherland JD, Barrio R.

PMID: 21689070





J Biol Chem. 2010 Aug 13;285(33):25841-9. Epub 2010 Jun 18.

Sumoylation modulates the activity of Spalt-like proteins during wing development in Drosophila.

Sánchez J, Talamillo A, Lopitz-Otsoa F, Pérez C, Hjerpe R, Sutherland JD, Herboso L, Rodríguez MS, Barrio R.

PMID: 20562097





Biochem Soc Trans. 2010 Feb;38(Pt 1):54-9.

SUMO and ubiquitin modifications during steroid hormone synthesis and function.

Talamillo A, Martín D, Hjerpe R, Sánchez J, Barrio R.

PMID: 20074035


Development. 2008 May;135(9):1659-68. Epub 2008 Mar 26.

Smt3 is required for Drosophila melanogaster metamorphosis.

Talamillo A, Sánchez J, Cantera R, Pérez C, Martín D, Caminero E, Barrio R.

PMID: 18367553



Other Laboratory Publications