在果蝇的中枢神经系统发育过程中,Hox 基因腹部 A 控制神经干细胞有丝分裂的及时进入和生长

RICHA ARYA, Papri Das, Smrithi Murthy, Eshan Abbas, Kristin White
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摘要

细胞的大小对其功能和生理非常重要。有趣的是,在克隆衍生的胚胎和造血干细胞中很容易观察到细胞大小的变化。在这里,我们研究了干细胞生长的调控及其与细胞命运的关联。我们在果蝇腹侧神经索(VNC)中观察到神经母细胞或神经干细胞(NSCs)的不同大小。特别是,胸部的神经干细胞比腹部的大。我们的研究发现了Hox基因腹部A(abdA)在调控腹部NSC生长中的重要作用。与胸腔NSCs相比,AbdA的发育表达会延缓它们的生长并推迟有丝分裂的进入。有针对性地缺失abdA可促进其生长,并使其更早进入有丝分裂期,加快循环速度。此外,abdA的异位表达缩小了胸腔NSCs的体积,并推迟了它们进入有丝分裂的时间。我们认为,abdA在调节NSC大小和退出静止期方面起着指导作用。这项研究首次证明了abdA通过调节NSC的生长、进入有丝分裂期和增殖率参与了NSC命运的决定,从而使它们有可能为中枢神经系统的模式化制造适当数量的后代。
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The Hox Gene, abdominal A controls timely mitotic entry of neural stem cell and their growth during CNS development in Drosophila
The size of a cell is important for its function and physiology. Interestingly, size variation can be easily observed in clonally derived embryonic and hematopoietic stem cells. Here, we investigated the regulation of stem cell growth and its association with cell fate. We observed heterogeneous sizes of neuroblasts or neural stem cells (NSCs) in the Drosophila ventral nerve cord (VNC). Specifically, thoracic NSCs were larger than those in the abdominal region of the VNC. Our research uncovered a significant role of the Hox gene abdominal A (abdA) in the regulation of abdominal NSC growth. Developmental expression of AbdA retards their growth and delays mitotic entry compared to thoracic NSCs. The targeted loss of abdA enhanced their growth and caused an earlier entry into mitosis with a faster cycling rate. Furthermore, ectopic expression of abdA reduced the size of thoracic NSCs and delayed their entry into mitosis. We suggest that abdA plays an instructive role in regulating NSC size and exit from quiescence. This study demonstrates for the first time the involvement of abdA in NSC fate determination by regulating their growth, entry into mitosis and proliferation rate, and thus their potential to make appropriate number of progeny for CNS patterning.
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