Lipids Control Stem Cell Division In The Brain

Scientists have discovered that enzymes involved in membrane lipid synthesis regulate asymmetric division in neural stem cells.

AsianScientist (Mar. 8, 2018) – A research group in Singapore and the US has demonstrated that asymmetric division of neural stem cells is controlled by the biosynthesis of membrane lipids. Their findings are published in the e-Life.

Stem cells are the basic material from which mature, specialized cells such as muscle and blood cells are produced. One way that stem cells replace old cells without depleting themselves is through asymmetric cell division. Through asymmetric division, a stem cell produces a new stem cell and another cell that undergoes differentiation to become a mature cell.

Studies on neural stem cells (NSCs) from fruit fly larvae have made huge contributions to the understanding of asymmetric division. Exploring the mechanisms underscoring asymmetric division is important because disruption of this process can result in excess NSC formation or failure to produce mature brain cells. This, in turn, can cause tumor formation or neurodevelopmental disorders.

While previous studies have established that a certain type of membrane lipids, called phosphatidylinositol (PI) lipids, is prevalent in various cell types, the role of PI lipids in asymmetric division of NSCs is not well understood.

In this study, scientists led by Associate Professor Wang Hongyan of the Duke-National University of Singapore Medical School sought to understand the role of PI lipids in fruit fly NSCs. They focused on two proteins critical for the biosynthesis of membrane lipids: phosphatidylinositol transfer proteins (PITPs) and PI4KIIIα.

These proteins were chosen because the counterparts of both proteins in mammals are associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, as well as various cancers. The team found a new role for a PITP protein called Vibrator, which together with PI4KIIIα, plays important roles in asymmetric division. They noted that the lipid binding and transfer activities of these proteins are particularly important for asymmetric division.

The team then mutated Vibrator and PI4KIIIα in flies, noting the neural defects arising from the loss of asymmetric division. When they introduced the mouse equivalents of Vibrator and PI4KIIIα proteins into the flies, the mouse proteins could partially alleviate the neural defects, suggesting that the mouse proteins perform similar functions in the mammalian brain.

The article can be found at: Koe et al. (2018) Vibrator and PI4KIIIα Govern Neuroblast Polarity by Anchoring Non-muscle Myosin II.


Source: Duke-NUS Medical School; Photo: Shutterstock.
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