State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, China.
Dev Dyn. 2023 Feb;252(2):263-275. doi: 10.1002/dvdy.534. Epub 2022 Sep 15.
In the zebrafish midbrain, GABAergic neurons develop from precursors located in the nucleus of the medial longitudinal fasciculus (nMLF). However, the precise mechanisms that underline generation of the nMLF GABAergic neuron are poorly understood.
GABAergic neurons in the nMLF co-express transcription factors tal2, gata2a, gata3, and nkx1.2lb. The Nodal-related gene and shh signaling are required for differentiation of nMLF GABAergic neuron precursors. Tal2 is important for nMLF GABAergic neurogenesis. Disruption of Tal2, embryos completely lack the GABA-synthesizing enzyme glutamic acid decarboxylase 67 gene (gad67) expressing cells in the nMLF, and the whole nkx1.2lb expressing cells in the midbrain. Although almost all tal2-expressing cells in the diencephalon and/or nMLF are gata2a- and gata3-positive, simultaneous knockdown of gata2a and gata3 does not affect either tal2 or gad67 expression.
In the zebrafish midbrain, expression of tal2, gata2a, and/or gata3 is independent of each other. The function of gata2a and gata3 is dispensable for generation of GABAergic neuron in the nMLF. This suggests that the functional connections of the regulatory genes leading to generation of nMLF GABAergic neurons have diverged between mouse and zebrafish.
在斑马鱼中脑，GABA 能神经元由位于中线纵束核（nMLF）的前体细胞发育而来。然而，产生 nMLF GABA 能神经元的精确机制还知之甚少。
nMLF 中的 GABA 能神经元共同表达转录因子 tal2、gata2a、gata3 和 nkx1.2lb。Nodal 相关基因和 Shh 信号通路对于 nMLF GABA 能神经元前体细胞的分化是必需的。Tal2 对于 nMLF GABA 能神经发生是重要的。Tal2 缺失的胚胎完全缺乏 nMLF 中表达谷氨酸脱羧酶 67 基因（gad67）的 GABA 合成酶表达细胞，以及整个中脑的 nkx1.2lb 表达细胞。尽管在间脑和/或 nMLF 中几乎所有的 tal2 表达细胞都呈 gata2a 和 gata3 阳性，但同时敲低 gata2a 和 gata3 并不影响 tal2 或 gad67 的表达。
在斑马鱼中脑，tal2、gata2a 和/或 gata3 的表达彼此独立。gata2a 和 gata3 的功能对于 nMLF GABA 能神经元的产生是可有可无的。这表明在产生 nMLF GABA 能神经元的调控基因的功能连接在小鼠和斑马鱼之间已经出现分歧。
