Making heads and tails of embryo development: lessons from the humble fly

MELBOURNE, TUESDAY 27 OCTOBER 2015: A member of a protein family that is usually associated with immune destruction of virally infected or cancerous cells has been found to control the release from cells of a critical growth factor governing head and tail development in fruit flies (Drosophila melanogaster). This may help explain how these perforin-like proteins function in human brain development and neurodevelopmental disorders such as Autism Spectrum Disorder.

The team believes their findings may provide new opportunities for the generation of novel therapeutics – for example, in the treatment of brain developmental disorders and conditions such as Autism Spectrum Disorder.

The research published today in Nature Communications was carried out at Monash University by postdoctoral researcher Dr Michelle Henstridge, Australian Research Council DECRA Fellow Dr Travis Johnson, and co-led by Associate Professor Coral Warr in the School of Biological Sciences and Professor James Whisstock in the Department of Biochemistry and Molecular Biology. Their research solves a long-standing question in developmental biology: how is the growth factor in the fly embryo controlled in order to determine where the head and tail form?

“These findings are significant and exciting as they suggest a completely new mechanism for how growth factor activity can be controlled,” Dr Johnson said.

Dr Henstridge added: “Understanding how growth factor activity is controlled is vital because loss of control of growth factors underlies many of the major diseases that afflict society, such as cancer and obesity.”

The perforin-like protein in the fruit fly is called ‘Torso-like’ because female flies lacking this protein produce embryos lacking heads and tails.

“The fruit fly Drosophila is a fantastic organism for investigating the question of how these perforin-like proteins act in embryo development; most of our knowledge of how human development and growth is regulated started with studies in the fruit fly. This is because most human genes controlling development and growth act in the same way in fruit flies,” Associate Professor Warr said.

Professor James Whisstock, who is also the Director of the Australian Research Council Centre of Excellence in Advanced Molecular Imaging, highlighted the significance of discovering that a protein related to the human immunity protein perforin – which punches holes in and kills foreign pathogen cells – is used to release a growth factor only at each end of the fly embryo.

“What’s exciting about our research is the discovery that a protein related to perforin – which usually functions to kill cells – is actually helping cells develop and differentiate in fly embryos. This is important because a group of perforin-like proteins found in the human brain have, in previous research, been shown to be associated with proper brain development,” Professor Whisstock said.

Associate Professor Warr added: “While we don’t yet know how these proteins work, we suspect they may also be involved in controlling growth factor release from cells.”

With support from a Monash University grant, they plan to continue to study fruit flies to explore the functions of important mammalian proteins on a much larger scale.

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The research was carried out using innovative microscopy and imaging techniques to observe how biological systems function at the molecular level. On this occasion the Olympus CV1000 laser scanning confocal microscope was used.

This was facilitated by the ARC Centre for Advanced Molecular Imaging whose Director is Professor James Whisstock at Monash University. The Centre brings together scientists from five Australian universities, as well as the University of Warwick (UK), the Australian Nuclear Science and Technology Organisation (ANSTO), synchrotrons in Australia and Germany and several high-tech companies.

Professor James Whisstock
Dr Michelle Henstridge

Stephanie Pradier
0424 568 314

The $39 million ARC-funded Imaging CoE develops and uses innovative imaging technologies to visualise the molecular interactions that underpin the immune system. Featuring an internationally renowned team of lead scientists across five major Australian Universities and academic and commercial partners globally, the Centre uses a truly multi scale and programmatic approach to imaging to deliver maximum impact.

The Imaging CoE is headquartered at Monash University with four collaborating organisations – La Trobe University, the University of Melbourne, University of New South Wales and the University of Queensland.

Image from top to bottom: 1. Embryo stained for markers of localised patterning. 2. Young embryo as seen under brightfield microscopy. 3. Confocal section of embryo expressing the growth factor required for patterning the head and tail. 4. Whole embryo confocal projection image. 5. Larva mutant for the torso-like gene with head and tail defects. 6. Normally patterned larva.