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Developmental biology - Cell Division|
What is asymmetric cell division?
Studies on neural stem cells (NSCs) in fruit fly larvae have made a huge contribution to our understanding of asymmetric cell division — important because disruptions in this process can result in excess NSCs and/or failure to produce mature brain cells. This in turn can cause tumours and/or neurodevelopmental disorders.
While previous studies established that a certain type of membrane lipid (fat) called phosphatidylinositol (PI) is involved in the asymmetry of several cell types, this process is still not well understood. In the new study, researchers wanted to precisely establish what role PI lipids play in developing fruit fly neural stem cells.
They focused on two proteins critical to the biosynthesis of two membrane lipids: (PITPs) and PI4KIIIa. Led by Associate Professor Wang Hongyan, Deputy Director of Neuroscience & Behavioral Disorders Program at Duke-NUS Medical School, Singapore, the team worked with a large group of collaborators from Texas A&A University in the United States, and the Mechanobiology Institute of the National University of Singapore.
The two proteins were chosen because counterparts to both exist in mammals and are associated with neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's, and even cancers.
Notably, her team found a new role for a PITP protein — called Vibrator — which acts along with PI4KIIIa to play an important role in the complex process of asymmetric cell division.
Her team also found evidence in the brains of mice, of protein counterparts which complement those phenotypic vibrator proteins found in flies. While this implies their research likely extends to mammals, further work will need to confirm if the roles of these proteins and lipids Wang's team identified are the same as those in mammals.
Neurodegenerative disorders such as Alzheimer's and cancers are still not well managed. Published in e-Life, the work by Professor Wang and her team contribute to our understanding of the molecular basis of these human disorders, and will aid in the development of future treatments. Just as importantly, their work increases our understanding of fundamental and vital biological processes.
A central feature of most stem cells is the ability to self-renew and undergo differentiation via asymmetric division. However, during asymmetric division the role of phosphatidylinositol (PI) lipids and their regulators is not well established. Here, we show that the sole type I PI transfer protein, Vibrator, controls asymmetric division of Drosophilaneural stem cells (NSCs) by physically anchoring myosin II regulatory light chain, Sqh, to the NSC cortex. Depletion of vib or disruption of its lipid binding and transfer activities disrupts NSC polarity. We propose that Vib stimulates PI4KIII? to promote synthesis of a plasma membrane pool of phosphatidylinositol 4-phosphate [PI(4)P] that, in turn, binds and anchors myosin to the NSC cortex. Remarkably, Sqh also binds to PI(4)P in vitro and both Vib and Sqh mediate plasma membrane localization of PI(4)P in NSCs. Thus, reciprocal regulation between Myosin and PI(4)P likely governs asymmetric division of NSCs.
Authors: Chwee Tat Koe, Ye Sing Tan, Max Lönnfors, Seong Kwon Hur, Christine Siok Lan Low, Yingjie Zhang, Pakorn Kanchanawong, Vytas A Bankaitis, Hongyan Wang.
Duke-NUS Medical School, Singapore Texas A&M University Health Science Center, United States National University of Singapore, Singapore
About Duke-NUS Medical School
The Duke-NUS Medical School (Duke-NUS) was established in 2005 as a strategic collaboration between the Duke University School of Medicine, located in North Carolina, USA, and the National University of Singapore (NUS). Duke-NUS offers a graduate-entry, 4-year MD (Doctor of Medicine) training programme based on the unique Duke model of education, with one year dedicated to independent study and research projects of a basic science or clinical nature. Duke-NUS also offers MD/PhD and PhD programmes. Duke-NUS has five Signature Research Programmes: Cancer and Stem Cell Biology, Neuroscience and Behavioural Disorders, Emerging Infectious Diseases, Cardiovascular and Metabolic Disorders, and Health Services and Systems Research.
Duke-NUS and SingHealth have established a strategic partnership in academic medicine that will guide and promote the future of medicine, tapping on and combining the collective strengths of SingHealth's clinical expertise and Duke-NUS' biomedical sciences research and medical education capabilities.
For more information, please visit http://www.duke-nus.edu.sg.
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Neural stem cells of fruit fly larvae: Controls in left panels.
GFP (Green Flourescent Protein) = green; DNA = blue.
(Top Right Panel) Vib- mutant lost membrane localization of myosin (Sqh-GFP) and accumulated membrane lipid PI(4)P-GFP (Bottom Right Panel) in the cytoplasm when compared to Controls.
Image credit: Chwee Tat Koe, Duke-NUS Medical School..