The Hox Gene, abdominal-A, controls the size and timely mitotic entry of neural stem cells during CNS patterning in Drosophila

Cell size is a critical determinant of its function and physiology. In this study, we investigated the regulation of stem cell size during Drosophila central nervous system (CNS) development and its association with cell fate. We note that neural stem cells (NSCs) in different regions of ventral nerve cord increase their size at different rates. The, thoracic NSCs grow at a faster rate compared to those in the abdominal region. We show that in addition to its role in apoptosis and nervous system remodeling, abdA also plays an instructive role in regulating the rate of NSC size increase and its timely entry into mitosis. Weak expression of abdA in larval abdominal NSCs was sufficient to retard the rate of their size increase and delay their mitotic entry compared to thoracic NSCs. Knockdown of abdA in NSCs enhances their rate of size increase leading to early mitotic entry, while ectopic abdA expression in thoracic NSCs reduces their size and delays their mitotic entry. We show that abdA-mediated NSC size regulation acts downstream of nutrition-induced NSC activation, which fine-tunes the stem cell potential spatiotemporally. This study highlights the instructive role of abdA in regulating various fates of larval NSCs during CNS patterning. Significance statementO_LIUnderstanding the upstream regulation of various aspects of the cell cycle is crucial; however, the influence of cell size on this process remains largely unknown. C_LIO_LIWe found an instructive role for the Hox gene abdominal A in maintaining the small size of neural stem cells (NSCs) and in regulating the time and rate of mitosis. C_LIO_LIThis mechanism is crucial because it helps NSCs generate the necessary number of neurons at an appropriate developmental stage, thereby contributing to proper central nervous system patterning. C_LI