Locus coeruleus neurons originate in alar rhombomere 1 and migrate into the basal plate:: Studies in chick and mouse embryos
Locus coeruleus neurons originate in alar rhombomere 1 and migrate into the basal plate:: Studies in chick and mouse embryos
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DOI：
10.1002/cne.20957
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发表时间：
2006-06-20
影响因子：
2.5
通讯作者：
Puelles, Luis
中科院分区：
文献类型：
--
作者：
Aroca, Pilar;Lorente-Canovas, Beatriz;Puelles, Luis
我们在小鼠和小鸡身上研究了蓝斑（LoC）的神经上皮起源和发育，蓝斑是大脑中最重要的去甲肾上腺素能神经元群。我们首先使用关键的去甲肾上腺素能标记基因 Dbh 和转录因子 Phox2a 和 Phox2b（Dbh 的上游）作为标记，研究了后脑中发育中的 LoC 的地形。在小鼠和鸡中，LoC 神经元首先沿着菱形核 1 (r1) 翼板的中间三分之一呈线性排列，与参考心室纵向带共线，该纵向带早期在 r2 翼板中表达 Phox2a 和 Phox2b，后来扩展到 r1。使用 LoC 标记（Dbh 或 Phox2a）和翼状（Pax7 和 Rnx3）或基底（Otp）遗传标记的双标记实验表明 LoC 细胞从翼状板中的起源迁移到侧基底板中的最终位置。为了通过实验证实这些建议并确定 LoC 的精确起源，我们通过使用鹌鹑雏鸡同位移植物绘制了 HH11 阶段雏鸡的 LoC 命运图谱。实验结果证实，LoC 起源于鼻翼板，遍及 r1 的鼻尾范围，并排除了鼻尾易位。他们还证实了 LoC 细胞向腹侧切向迁移到外侧基底板，即迁移后 LoC 原基所在的位置。与邻近的 alar r1 衍生细胞群的比较表明，LoC 神经元起源于小脑外部，位于预期前庭柱和三叉神经柱来源之间背腹侧插入的基质区域中。
We investigated in the mouse and chick the neuroepithelial origin and development of the locus coeruleus (LoC), the most important noradrenergic neuronal population in the brain. We first studied the topography of the developing LoC in the hindbrain, using as markers the key noradrenergic marker gene Dbh and the transcription factors Phox2a and Phox2b (upstream of Dbh). In both mouse and chicken, LoC neurons first appear arranged linearly along the middle one-third of the alar plate of rhombomere 1 (r1), collinear to a reference ventricular longitudinal band that early on expresses Phox2a and Phox2b in the alar plate of r2 and later expands to r1. Double-labeling experiments with LoC markers (Dbh or Phox2a) and either alar (Pax7 and Rnx3) or basal (Otp) genetic markers suggested that LoC cells migrate from their origin in the alar plate to a final position in the lateral basal plate. To corroborate these suggestions experimentally and determine the precise origin of the LoC, we fate mapped the LoC in the chick at stage HH11 by using quail-chick homotopic grafts. The experimental results confirmed that the LoC originates in the alar plate throughout the rostrocaudal extent of r1 and ruled out a rostrocaudal translocation. They also corroborated a ventralward tangential migration of LoC cells into the lateral basal plate, where the postmigratory LoC primordium is located. Comparisons with neighboring alar r1-derived cell populations established that LoC neurons originate outside the cerebellum, in a matrix area intercalated dorsoventrally between the sources of the prospective vestibular and trigerninal columns.