MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, United Kingdom.
Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19895-900. doi: 10.1073/pnas.0910894106. Epub 2009 Nov 10.
During vertebrate brain development, the onset of neuronal differentiation is under strict temporal control. In the mammalian thalamus and other brain regions, neurogenesis is regulated also in a spatially progressive manner referred to as a neurogenetic gradient, the underlying mechanism of which is unknown. Here we describe the existence of a neurogenetic gradient in the zebrafish thalamus and show that the progression of neurogenesis is controlled by dynamic expression of the bHLH repressor her6. Members of the Hes/Her family are known to regulate proneural genes, such as Neurogenin and Ascl. Here we find that Her6 determines not only the onset of neurogenesis but also the identity of thalamic neurons, marked by proneural and neurotransmitter gene expression: loss of Her6 leads to premature Neurogenin1-mediated genesis of glutamatergic (excitatory) neurons, whereas maintenance of Her6 leads to Ascl1-mediated production of GABAergic (inhibitory) neurons. Thus, the presence or absence of a single upstream regulator of proneural gene expression, Her6, leads to the establishment of discrete neuronal domains in the thalamus.
在脊椎动物大脑发育过程中，神经元分化的开始受到严格的时间控制。在哺乳动物丘脑和其他大脑区域中，神经发生也受到空间渐进方式的调节，称为神经发生梯度，其潜在机制尚不清楚。在这里，我们描述了斑马鱼丘脑存在神经发生梯度，并表明神经发生的进展受 bHLH 抑制因子 her6 的动态表达控制。众所周知，Hes/Her 家族成员调节神经前体细胞基因，如 Neurogenin 和 Ascl。在这里，我们发现 Her6 不仅决定了神经发生的开始，还决定了丘脑神经元的身份，其特征是神经前体细胞和神经递质基因的表达：缺失 Her6 导致过早的谷氨酸能（兴奋性）神经元由 Neurogenin1 介导产生，而维持 Her6 导致 GABA 能（抑制性）神经元由 Ascl1 介导产生。因此，单个上游神经前体细胞基因表达调节因子 Her6 的存在或缺失导致了丘脑中离散神经元区域的建立。
