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

Cortex glia in Drosophila central nervous system forms a niche around neural cells for necessary signals to establish cross-talk with their surroundings. These cells grow and expand their thin processes around neural cell bodies. Although essential for the development and function of the nervous system, how these cells make extensive and intricate connected networks remain largely unknown. Here we show that Cut, a homeodomain transcription factor, directly regulates the fate of the cortex glia, impacting NSC homeostasis. Focusing on the thoracic ventral nerve cord (tVNC), we found that Cut is required for normal growth and development of cortex glia and timely increase in DNA content to undergo endomitosis. Knockdown of Cut in cortex glia significantly reduces the growth of cellular processes, the network around NSCs, and their progenys cell bodies. Conversely, overexpression of Cut induces overall growth of the main processes at the expense of side ones. Whereas the Cut knockdown slowdown the timely increase of DNA, Cut overexpression results in a significant increase in nuclear size and volume and a threefold increase in DNA content of cortex glia. Further, we note that constitutively high Cut also interfered with nuclei separation during endomitosis. Since cortex glia form syncytial networks around neural cells, the finding identifies Cut as a novel regulator of glial growth and endomitosis to support a functional nervous system. Article SummaryCut homeodomain transcription factor is crucial for cortex glia growth and the formation of complex cellular processes around neural cells. This regulation ensures a timely increase in DNA content, allowing the cells to enter endomitosis. Constitutively high Cut levels increase the DNA content of these cells to several folds. The finding emphasizes the need to investigate if activated CUX1, the human homolog of Cut, in glioma enhances chromosomal instability and, in conjunction with other mutations, enhances their tumorigenic potential.