The Hippo signalling pathway coordinates organ growth and limits developmental variability by controlling dilp8...

Area of Science:

• Developmental biology
• Genetics
• Endocrinology

Background:

• Coordinated organ growth is essential for proper development and organismal fitness.
• Drosophila Dilp8 (Drosophila insulin-like peptide 8) is a hormone linking organ growth to maturation and developmental stability.
• The regulatory signals controlling Dilp8 activity remain largely unknown.

Purpose of the Study:

• To identify the upstream regulators of Dilp8 expression during normal development.
• To elucidate the role of the Hippo pathway in controlling Dilp8 and developmental stability.

Main Methods:

• Investigated the regulation of the dilp8 promoter by Hippo pathway components.
• Utilized genome editing to mutate a putative Hpo-responsive element (HRE) in the dilp8 promoter.
• Assessed developmental stability by measuring fluctuating asymmetry (FA) in mutant flies.

Main Results:

• Yorkie (Yki) and Scalloped (Sd), key components of the Hippo pathway, directly regulate dilp8 transcription.
• A Hpo-responsive element (HRE) in the dilp8 promoter mediates this regulation.
• Genome editing of the HRE leads to increased fluctuating asymmetry, phenocopying dilp8 loss-of-function.

Conclusions:

• The Hippo pathway, via Yki/Sd, directly controls dilp8 expression.
• This regulation connects organ growth status to developmental stability through a feedback loop involving Hpo and Dilp8 signaling.
• Dilp8 plays a crucial role in maintaining developmental stability by integrating growth signals.