PDF(Pubmed)
Abstract：
BACKGROUND: A key step in nervous system development involves the coordinated control of neural progenitor specification and positioning. A long-standing model for the vertebrate CNS postulates that transient anatomical compartments - known as neuromeres - function to position neural progenitors along the embryonic anteroposterior neuraxis. Such neuromeres are apparent in the embryonic hindbrain - that contains six rhombomeres with morphologically apparent boundaries - but other neuromeres lack clear morphological boundaries and have instead been defined by different criteria, such as differences in gene expression patterns and the outcomes of transplantation experiments. Accordingly, the caudal hindbrain (CHB) posterior to rhombomere (r) 6 has been variably proposed to contain from two to five \'pseudo-rhombomeres\', but the lack of comprehensive molecular data has precluded a detailed definition of such structures.
METHODS: We used single-cell Multiome analysis, which allows simultaneous characterization of gene expression and chromatin state of individual cell nuclei, to identify and characterize CHB progenitors in the developing zebrafish CNS.
RESULTS: We identified CHB progenitors as a transcriptionally distinct population, that also possesses a unique profile of accessible transcription factor binding motifs, relative to both r6 and the spinal cord. This CHB population can be subdivided along its dorsoventral axis based on molecular characteristics, but we do not find any molecular evidence that it contains multiple pseudo-rhombomeres. We further observe that the CHB is closely related to r6 at the earliest embryonic stages, but becomes more divergent over time, and that it is defined by a unique gene regulatory network.
CONCLUSIONS: We conclude that the early CHB represents a single neuromere compartment that cannot be molecularly subdivided into pseudo-rhombomeres and that it may share an embryonic origin with r6.
METHODS: We used single-cell Multiome analysis, which allows simultaneous characterization of gene expression and chromatin state of individual cell nuclei, to identify and characterize CHB progenitors in the developing zebrafish CNS.
RESULTS: We identified CHB progenitors as a transcriptionally distinct population, that also possesses a unique profile of accessible transcription factor binding motifs, relative to both r6 and the spinal cord. This CHB population can be subdivided along its dorsoventral axis based on molecular characteristics, but we do not find any molecular evidence that it contains multiple pseudo-rhombomeres. We further observe that the CHB is closely related to r6 at the earliest embryonic stages, but becomes more divergent over time, and that it is defined by a unique gene regulatory network.
CONCLUSIONS: We conclude that the early CHB represents a single neuromere compartment that cannot be molecularly subdivided into pseudo-rhombomeres and that it may share an embryonic origin with r6.
摘要：
背景：神经系统发育的关键步骤涉及神经祖细胞规格和定位的协调控制。脊椎动物中枢神经系统的长期模型假设，瞬时解剖区室-称为神经细胞-具有沿着胚胎前后神经轴定位神经祖细胞的功能。这种神经细胞在胚胎后脑中很明显-包含六个形态上明显的菱形-但其他神经细胞缺乏明确的形态边界，而是由不同的标准定义。例如基因表达模式和移植实验结果的差异。因此，菱形（r）6后面的后脑（CHB）已被可变地提议包含2至5个“伪菱形”，但是缺乏全面的分子数据排除了对这种结构的详细定义。
方法：我们使用单细胞多体组分析，可以同时表征单个细胞核的基因表达和染色质状态，在发育中的斑马鱼CNS中鉴定和表征CHB祖细胞。
结果：我们将CHB祖细胞鉴定为转录上不同的群体，它还具有可接近的转录因子结合基序的独特概况，相对于r6和脊髓。这种CHB群体可以细分沿其背腹轴的基础上的分子特征，但是我们没有发现任何分子证据表明它含有多个伪菱形。我们进一步观察到CHB在最早的胚胎阶段与r6密切相关，但随着时间的推移变得更加分歧，它是由独特的基因调控网络定义的。
结论：我们得出结论，早期CHB代表一个单一的神经区室，不能被分子细分为假菱形，它可能与r6共享胚胎起源。
方法：我们使用单细胞多体组分析，可以同时表征单个细胞核的基因表达和染色质状态，在发育中的斑马鱼CNS中鉴定和表征CHB祖细胞。
结果：我们将CHB祖细胞鉴定为转录上不同的群体，它还具有可接近的转录因子结合基序的独特概况，相对于r6和脊髓。这种CHB群体可以细分沿其背腹轴的基础上的分子特征，但是我们没有发现任何分子证据表明它含有多个伪菱形。我们进一步观察到CHB在最早的胚胎阶段与r6密切相关，但随着时间的推移变得更加分歧，它是由独特的基因调控网络定义的。
结论：我们得出结论，早期CHB代表一个单一的神经区室，不能被分子细分为假菱形，它可能与r6共享胚胎起源。
