Cut homeodomain transcription factor is a novel regulator of cortical glia morphogenesis and niche maintenance around neural stem cells

Abstract

AbstractCortical glia inDrosophilacentral nervous system forms a niche around neural stem cells (NSCs) and their progeny for necessary signals to establish cross-talk with their surroundings. These cells grow and expand their thin cytoplasmic extensions around neural cell bodies in the nervous system. Although essential for the development and function of the nervous system, how these cells make extensive and intricate membrane networks remain largely unknown. Here we show that Cut, a homeodomain transcription factor, directly regulates the fate of the cortical glial cells impacting NSC homeostasis. Focusing on the thoracic ventral nerve cord (tVNC), we found that Cut is required for normal growth and development of cortical glial cells. We also highlight that levels of Cut expression play an essential role in the cytoplasmic membrane network growth around the neural cells. Loss of Cut in cortical glia results in a substantial reduction in their cytoplasmic extensions and network around cell bodies of NSCs and their progeny, whereas its overexpression induces the overall growth of cortical glia main branches at the expense of side ones. We also note a striking gain in the nuclear size and volume of cortical glial cells upon Cut overexpression. Furthermore, constitutively high Cut levels increase DNA content in these cells more than threefold, indicating an interference with the splitting of nuclei during endomitosis. Since cortical glia makes syncytial membrane networks around neural cells, the finding identifies Cut as a regulator of glial growth and endomitosis to support a functional nervous system. It is the first report that highlights a novel function of Cut in regulating the growth and branching of cortical glial cells and control over endomitosis.HighlightsIn this study, we have investigated the role of homeodomain transcription factor Cut in the growth and development of cortical glial cells. We found that Cut regulates cortical glial growth and the formation of complex membrane network around the neural cells. We also note that constitutive high Cut levels in these cells interfere with their normal endomitosis process, decrease nuclei number, and affect glial growth. Thus, Cut is a novel player that regulates the dynamic growth of cortical glial niche around neural cells. Since the human homolog of Cut, CUX1 is considered one of the cancer driver genes which is highly expressed in glioma, our finding highlights the need to explore if activated CUX1 in these tumors enhances chromosomal instability in glial cells and, in conjunction with other mutations, enhances their tumorigenic potential.