Hamid Aisha, Gutierrez Andrew, Munroe Jordan, Syed Mubarak Hussain
Department of Biology, University of New Mexico, Albuquerque, NM 87113, USA.
Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
Semin Cell Dev Biol. 2023 Jun;142:23-35. doi: 10.1016/j.semcdb.2022.07.007. Epub 2022 Jul 29.
Proper functioning of the nervous system relies not only on the generation of a vast repertoire of distinct neural cell types but also on the precise neural circuitry within them. How the generation of highly diverse neural populations is regulated during development remains a topic of interest. Landmark studies in Drosophila have identified the genetic and temporal cues regulating neural diversity and thus have provided valuable insights into our understanding of temporal patterning of the central nervous system. The development of the Drosophila central complex, which is mostly derived from type II neural stem cell (NSC) lineages, showcases how a small pool of NSCs can give rise to vast and distinct progeny. Similar to the human outer subventricular zone (OSVZ) neural progenitors, type II NSCs generate intermediate neural progenitors (INPs) to expand and diversify lineages that populate higher brain centers. Each type II NSC has a distinct spatial identity and timely regulated expression of many transcription factors and mRNA binding proteins. Additionally, INPs derived from them show differential expression of genes depending on their birth order. Together type II NSCs and INPs display a combinatorial temporal patterning that expands neural diversity of the central brain lineages. We cover advances in current understanding of type II NSC temporal patterning and discuss similarities and differences in temporal patterning mechanisms of various NSCs with a focus on how cell-intrinsic and extrinsic hormonal cues regulate temporal transitions in NSCs during larval development. Cell extrinsic ligands activate conserved signaling pathways and extrinsic hormonal cues act as a temporal switch that regulate temporal progression of the NSCs. We conclude by elaborating on how a progenitor's temporal code regulates the fate specification and identity of distinct neural types. At the end, we also discuss open questions in linking developmental cues to neural identity, circuits, and underlying behaviors in the adult fly.
神经系统的正常运作不仅依赖于大量不同神经细胞类型的产生，还依赖于其中精确的神经回路。在发育过程中，高度多样化的神经群体是如何产生的，仍然是一个备受关注的话题。果蝇的标志性研究已经确定了调节神经多样性的遗传和时间线索，从而为我们理解中枢神经系统的时间模式提供了有价值的见解。果蝇中央复合体的发育主要源自II型神经干细胞（NSC）谱系，它展示了一小群NSC如何产生大量不同的后代。与人类外侧脑室下区（OSVZ）神经祖细胞类似，II型NSC产生中间神经祖细胞（INP），以扩展和多样化填充更高脑区的谱系。每个II型NSC都有独特的空间身份以及许多转录因子和mRNA结合蛋白的适时调控表达。此外，从它们衍生而来的INP根据其出生顺序表现出基因的差异表达。II型NSC和INP共同展示了一种组合时间模式，扩展了中枢脑谱系的神经多样性。我们涵盖了目前对II型NSC时间模式的理解进展，并讨论了各种NSC时间模式机制的异同，重点关注细胞内在和外在激素线索如何在幼虫发育过程中调节NSC的时间转变。细胞外配体激活保守的信号通路，外在激素线索充当调节NSC时间进程的时间开关。我们通过阐述祖细胞的时间编码如何调节不同神经类型的命运特化和身份来得出结论。最后，我们还讨论了将发育线索与成年果蝇的神经身份、回路和潜在行为联系起来的开放性问题。
