Jain S, Zipursky S L
Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Semin Cell Dev Biol. 2023 Jun;142:81-90. doi: 10.1016/j.semcdb.2022.05.012. Epub 2022 May 26.
Wiring an animal brain is a complex process involving a staggering number of cell-types born at different times and locations in the developing brain. Incorporation of these cells into precise circuits with high fidelity is critical for animal survival and behavior. Assembly of neuronal circuits is heavily dependent upon proper timing of wiring programs, requiring neurons to express specific sets of genes (sometimes transiently) at the right time in development. While cell-type specificity of genetic programs regulating wiring has been studied in detail, mechanisms regulating proper timing and coordination of these programs across cell-types are only just beginning to emerge. In this review, we discuss some temporal regulators of wiring programs and how their activity is controlled over time and space. A common feature emerges from these temporal regulators - they are induced by cell-extrinsic cues and control transcription factors capable of regulating a highly cell-type specific set of target genes. Target specificity in these contexts comes from cell-type specific transcription factors. We propose that the spatiotemporal specificity of wiring programs is controlled by the combinatorial activity of temporal programs and cell-type specific transcription factors. Going forward, a better understanding of temporal regulators will be key to understanding the mechanisms underlying brain wiring, and will be critical for the development of in vitro models like brain organoids.
连接动物大脑是一个复杂的过程,涉及在发育中的大脑不同时间和位置产生的数量惊人的细胞类型。将这些细胞高保真地整合到精确的神经回路中对动物的生存和行为至关重要。神经回路的组装严重依赖于布线程序的正确时间安排,这要求神经元在发育的正确时间表达特定的基因集(有时是瞬时表达)。虽然调节布线的遗传程序的细胞类型特异性已得到详细研究,但调节这些程序在不同细胞类型之间的正确时间安排和协调的机制才刚刚开始显现。在这篇综述中,我们讨论了一些布线程序的时间调节因子,以及它们的活性如何随时间和空间受到控制。这些时间调节因子有一个共同特征——它们由细胞外信号诱导,并控制能够调节一组高度细胞类型特异性靶基因的转录因子。在这些情况下,靶标特异性来自细胞类型特异性转录因子。我们提出,布线程序的时空特异性由时间程序和细胞类型特异性转录因子的组合活性控制。展望未来,更好地理解时间调节因子将是理解大脑布线潜在机制的关键,并且对于像脑类器官这样的体外模型的开发至关重要。