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Fruit flies help uncover tumor-preventing protein complex

12 March 2014 – A team of researchers from Duke-NUS Graduate Medical School have discovered a protein complex that disrupts the process known as dedifferentiation[1], known to promote tumour development.

Dedifferentiation (reversion) is a process that leads progenitor [2] or mature cells to become ‘ectopic neural stem cells’ which causes tumors. By detecting this protein complex, Duke-NUS researchers have shed light on a process that inhibits tumor development and gives hope for the discovery of therapies and treatments that target tumor prevention through this pathway. 

Researchers study neural stem cells (NSC) or ‘neuroblasts’ in the larval brains of fruit flies in order to better understand stem cell behavior in the lab. NSCs are multi-potent cells key to the function of the body’s brain and nervous system. In the Neuroscience and Behavioral Disorders Program laboratory at Duke-NUS, ‘type II’ neuroblasts, found in fruit flies that are especially similar to human NSCs, are studied.

Type II neuroblasts, like stem cells, divide to generate another neuroblast and a second cell which are the progenitor cells. These cells can then undergo differentiation - the process they undergo to become specific types of cells. However, progenitor cells are prone to dedifferentiate into NSCs and become ‘ectopic NSCs’. When this happens, ‘ectopic NSCs’ can undergo uncontrolled growth, leading to brain tumor development.

Asst Professor Hongyan Wang led her team, using the fruit fly (Drosophila melanogaster) model, to uncover how a protein complex, composed of Brahma, HDAC3 and Earmuff, plays an important role in preventing the progenitor cells from undergoing dedifferentiation. These findings have provided a critical and novel insight into a process that was previously poorly understood, and have implications for the overall understanding of NSCs and for the development of future cancer therapies.

Published online in eLIFE on March 11, 2014, the research is supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Research Fellowship (NRF-RF2009-02) and the Duke-NUS Signature Research Program, with funding from Singapore’s Agency for Science, Technology, and Research and the Ministry of Health.

 

 

 

 

 

 

 

 

Pictured here are ectopic neural stem cells formed from dedifferentiation of progenitor cells upon loss of both HDAC3 and Snr1 (a subunit of the Brahma complex).

[1]Differentiation is a process that progenitor cells in the nervous system undergo to become specific types of cells such as neurons and glial cells that are crucial to proper brain functions. Dedifferentiation, on the other hand, is what happens when these cells instead revert back to neural stem cells, which is a more primitive state. This is problematic as it can lead to tumor development.

[2]Progenitor or mature cells are generated from neural stem cells or ‘neuroblasts’, thereby rendering them more specific and ready to differentiate than stem cells.