Dev cell: how Zika virus causes microcephaly

November 18, 2019 / BIOON / -- a new study led by researchers at Baylor Medical College reveals how Zika virus infection causes microcephaly in newborns The team found that Zika virus protein NS4A disrupts brain growth by hijacking and regulating the production of new neurons These findings point to the possibility of developing treatment strategies to prevent microcephaly associated with Zika virus infection The research was recently published in the journal developmental cell The team learned that Zika virus infection in the uterus can cause microcephaly in newborns, so they studied the possibility of Zika virus mediated its role in the brain through ankle2 (image source: www Pixabay Com) in a subsequent Drosophila study, the researchers demonstrated that overexpression of Zika protein NS4A causes microcephaly symptoms in Drosophila by inhibiting the function of ankle2, a cell cycle regulator that plays a role by inhibiting the activity of VRK1 protein Since little is known about the role of ankle2 or VRK1 in brain development, Bellen and his colleagues have used a variety of methods to understand the exact mechanism of ankle2 related microcephaly The team found that Drosophila larvae with the ankle2 mutation had smaller brains and significantly fewer neuroblasts (brain cell precursors) that could not mature The normal expression of ankle2 gene in mutant larvae can repair all previous defects Dr Nichole link, postdoctoral researcher and the first author of the paper, said: "to understand why ankle2 mutant has fewer neuroblasts and a much smaller brain, we have studied in-depth asymmetric cell division, which is a basic process of generating and maintaining neuroblasts (also known as neural stem cells) in the brains of Drosophila and human beings." Asymmetric cell division is a precisely regulated process by which neuroblasts produce two different cell types One is a copy of a neuron, the other is a cell programmed to become a different type of cell, such as a neuron or glial cell The correct asymmetric distribution and division of these cells is essential for normal brain development, because they need to generate the correct number of neurons, different neuronal lineages and supplement them into "pools" of neurons for further division "When the content of ankle2 in Drosophila decreased, the key proteins (such as par complex protein and Miranda) were mislabelled in the adult cells of larva In addition, the real-time imaging analysis of these neural cells showed that the cell division was defective or incomplete These results indicate that ankle2 is a key regulator of asymmetric cell division Further analysis revealed more details about how ankle2 regulates asymmetric neuroblastoma They found that ankle2 protein interacted with VRK1 kinase, and the ankle2 mutant altered this interaction by disrupting asymmetric cell division "Linking our findings with Zika virus related microcephaly, we found that expression of Zika virus protein NS4A in Drosophila can lead to microcephaly by hijacking ankle2 / VRK1, a key component of asymmetric neuroblastoma cell division This explains why severe microcephaly, manifested as intrauterine Zika virus infection in infants, was observed in patients with genetic defects similar to ankle2 / VRK1 " In D Clark, Ghayda M Mirzaa, James R Lupski, Hugo J Bellen Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly Developmental Cell , 2019; DOI: 10.1016/j.devcel.2019.10.009