Sellers Katherine, Zyka Verena, Lumsden Andrew G, Delogu Alessio
MRC Centre for Developmental Neurobiology, King's College London, London SE1 1UL, UK.
Neural Dev. 2014 Jun 15;9:14. doi: 10.1186/1749-8104-9-14.
The thalamus is often defined as the 'gateway to consciousness', a feature that is supported by the specific connectivity and electrophysiological properties of its neurons. Inhibitory GABAergic neurons are required for the dynamic gating of information passing through the thalamus. The high degree of heterogeneity among thalamic GABA neurons suggests that, during embryonic development, alternative differentiation programmes exist to guide the acquisition of inhibitory neuron subtype identity.
Taking advantage of the accessibility of the developing chick embryo, we have used in ovo manipulations of gene expression to test the role of candidate transcription factors in controlling GABAergic neuronal subtype identity in the developing thalamus.
In this study, we describe two alternative differentiation programmes for GABAergic neurogenesis in the thalamus and identify Helt and Dlx2 as key transcription factors that are sufficient to direct neuronal progenitors along a specific differentiation pathway at the expense of alternative lineage choices. Furthermore, we identify Calb2, a gene encoding for the GABA subtype marker calretinin as a target of the transcription factor Sox14. This work is a step forward in our understanding of how GABA neuron diversity in the thalamus is achieved during development and will help future investigation of the molecular mechanisms that lead up to the acquisition of different synaptic targets and electrophysiological features of mature thalamic inhibitory neurons.
丘脑常被定义为“意识的门户”,这一特征由其神经元的特定连接性和电生理特性所支持。抑制性γ-氨基丁酸能(GABAergic)神经元是信息通过丘脑进行动态门控所必需的。丘脑GABA神经元之间的高度异质性表明,在胚胎发育过程中,存在替代分化程序来指导抑制性神经元亚型身份的获得。
利用发育中的鸡胚易于操作的特点,我们通过在鸡胚内对基因表达进行操作,来测试候选转录因子在控制发育中的丘脑GABA能神经元亚型身份方面的作用。
在本研究中,我们描述了丘脑GABA能神经发生的两种替代分化程序,并确定Helt和Dlx2为关键转录因子,它们足以引导神经元祖细胞沿着特定的分化途径分化,同时牺牲替代谱系选择。此外,我们确定Calb2(一种编码GABA亚型标志物钙视网膜蛋白的基因)是转录因子Sox14的一个靶标。这项工作在我们理解丘脑GABA神经元多样性在发育过程中如何实现方面向前迈进了一步,并将有助于未来对导致成熟丘脑抑制性神经元获得不同突触靶点和电生理特征的分子机制的研究。