Hirsch Dana, Kohl Ayelet, Wang Yuan, Sela-Donenfeld Dalit
Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
Front Neuroanat. 2021 Dec 24;15:793161. doi: 10.3389/fnana.2021.793161. eCollection 2021.
Unraveling the inner workings of neural circuits entails understanding the cellular origin and axonal pathfinding of various neuronal groups during development. In the embryonic hindbrain, different subtypes of dorsal interneurons (dINs) evolve along the dorsal-ventral (DV) axis of rhombomeres and are imperative for the assembly of central brainstem circuits. dINs are divided into two classes, class A and class B, each containing four neuronal subgroups (dA1-4 and dB1-4) that are born in well-defined DV positions. While all interneurons belonging to class A express the transcription factor Olig3 and become excitatory, all class B interneurons express the transcription factor Lbx1 but are diverse in their excitatory or inhibitory fate. Moreover, within every class, each interneuron subtype displays its own specification genes and axonal projection patterns which are required to govern the stage-by-stage assembly of their connectivity toward their target sites. Remarkably, despite the similar genetic landmark of each dINs subgroup along the anterior-posterior (AP) axis of the hindbrain, genetic fate maps of some dA/dB neuronal subtypes uncovered their contribution to different nuclei centers in relation to their rhombomeric origin. Thus, DV and AP positional information has to be orchestrated in each dA/dB subpopulation to form distinct neuronal circuits in the hindbrain. Over the span of several decades, different axonal routes have been well-documented to dynamically emerge and grow throughout the hindbrain DV and AP positions. Yet, the genetic link between these distinct axonal bundles and their neuronal origin is not fully clear. In this study, we reviewed the available data regarding the association between the specification of early-born dorsal interneuron subpopulations in the hindbrain and their axonal circuitry development and fate, as well as the present existing knowledge on molecular effectors underlying the process of axonal growth.
揭示神经回路的内部运作机制需要了解发育过程中各种神经元群体的细胞起源和轴突寻路。在胚胎后脑，背侧中间神经元（dINs）的不同亚型沿菱脑节的背腹（DV）轴演化，对中枢脑干回路的组装至关重要。dINs分为A类和B类，每类包含四个神经元亚群（dA1 - 4和dB1 - 4），它们在明确的DV位置产生。虽然所有属于A类的中间神经元都表达转录因子Olig3并成为兴奋性神经元，但所有B类中间神经元都表达转录因子Lbx1，但其兴奋性或抑制性命运各不相同。此外，在每一类中，每个中间神经元亚型都显示出其自身的特异性基因和轴突投射模式，这些是控制其向靶位点连接的逐步组装所必需的。值得注意的是，尽管每个dINs亚群在后脑前后（AP）轴上具有相似的遗传标记，但一些dA/dB神经元亚型的遗传命运图谱揭示了它们相对于菱脑节起源对不同核中心的贡献。因此，必须在每个dA/dB亚群中协调DV和AP位置信息，以在后脑形成不同的神经元回路。在几十年的时间里，不同的轴突路径已被充分记录，它们在整个后脑的DV和AP位置动态出现并生长。然而，这些不同轴突束与其神经元起源之间的遗传联系尚不完全清楚。在本研究中，我们回顾了关于后脑早期出生的背侧中间神经元亚群的特化与其轴突回路发育和命运之间关联的现有数据，以及目前关于轴突生长过程中分子效应器的现有知识。
