Neural Stem Cell Reactivation in Cultured Drosophila Brain Explants.
Neural Stem Cell Reactivation in Cultured Drosophila Brain Explants.
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DOI：
10.3791/63189
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发表时间：
2022-05-18
影响因子：
1.2
通讯作者：
Siegrist, Sarah E.
中科院分区：
文献类型：
--
作者：
Keliinui, Cami Naomi;Doyle, Susan E.;Siegrist, Sarah E.
神经干细胞具有增殖、分化、凋亡甚至进入和退出静止期的能力。这些过程中有许多是由NSC内在遗传程序与NSC外在因素（局部和系统）之间复杂的相互作用控制的。在遗传学模式生物黑腹果蝇中，神经干细胞（称为神经母细胞（NB））在胚胎向幼虫转变期间从静止转变为增殖。在这段时间里，幼虫从蛋壳中出来，开始爬行，寻找食物营养。作为对动物进食的反应，脂肪体（一种具有脂质储存能力的内分泌器官）产生信号，该信号被全身释放到循环血淋巴中。响应于脂肪体衍生信号（FBDS），果蝇胰岛素样肽（Dilps）从脑神经分泌神经元和神经胶质细胞产生和释放，导致NB及其神经胶质和气管生态位中的PI3激酶生长信号的下游激活。虽然这是NBs如何从静止到增殖转换的当前模型，但FBDS外在线索的性质仍然难以捉摸。为了更好地了解NB外部系统性线索如何调节从静止退出，开发了一种在动物喂养前体外培养早期幼虫脑的方法。用这种方法，可以向培养基中提供外源因子，并测定NB从静止状态中的退出。我们发现，外源性胰岛素足以重新激活NBs从静止的全脑外植体。因为这种方法是非常适合大规模的屏幕，我们的目标是确定额外的外在线索，调节NB静止与增殖的决定。由于调节NSC增殖决定的基因和途径在进化上是保守的，因此该试验的结果可以为改善临床再生疗法提供见解。
Neural stem cells (NSCs) have the ability to proliferate, differentiate, undergo apoptosis, and even enter and exit quiescence. Many of these processes are controlled by the complex interplay between NSC intrinsic genetic programs with NSC extrinsic factors, local and systemic. In the genetic model organism, Drosophila melanogaster, NSCs, known as neuroblasts (NBs), switch from quiescence to proliferation during the embryonic to larval transition. During this time, larvae emerge from their eggshells and begin crawling, seeking out dietary nutrients. In response to animal feeding, the fat body, an endocrine organ with lipid storage capacity, produces a signal, which is released systemically into the circulating hemolymph. In response to the fat body-derived signal (FBDS), Drosophila insulin-like peptides (Dilps) are produced and released from brain neurosecretory neurons and glia, leading to downstream activation of PI3-kinase growth signaling in NBs and their glial and tracheal niche. Although this is the current model for how NBs switch from quiescence to proliferation, the nature of the FBDS extrinsic cue remains elusive. To better understand how NB extrinsic systemic cues regulate exit from quiescence, a method was developed to culture early larval brains in vitro before animal feeding. With this method, exogenous factors can be supplied to the culture media and NB exit from quiescence assayed. We found that exogenous insulin is sufficient to reactivate NBs from quiescence in whole-brain explants. Because this method is well-suited for large-scale screens, we aim to identify additional extrinsic cues that regulate NB quiescence versus proliferation decisions. Because the genes and pathways that regulate NSC proliferation decisions are evolutionarily conserved, results from this assay could provide insight into improving regenerative therapies in the clinic.
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影响因子：
11.8
作者：
Wosczyna MN;Rando TA
通讯作者：
Rando TA
果蝇中饮食中的无眼无眼蘑菇体神经细胞增殖。
影响因子：
7.7
作者：
Sipe CW;Siegrist SE
通讯作者：
Siegrist SE
影响因子：
1.2
作者：
Prithviraj, Ranjini;Trunova, Svetlana;Giniger, Edward
通讯作者：
Giniger, Edward
影响因子：
9.8
作者：
Yuan, Xin;Sipe, Conor W.;Siegrist, Sarah E.
通讯作者：
Siegrist, Sarah E.
影响因子：
9.2
作者：
Lin, Suewei;Marin, Elizabeth C.;Lee, Tzumin
通讯作者：
Lee, Tzumin