Alqadah Amel, Hsieh Yi-Wen, Vidal Berta, Chang Chieh, Hobert Oliver, Chuang Chiou-Fen
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA Molecular and Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, OH, USA.
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA.
EMBO J. 2015 Oct 14;34(20):2574-89. doi: 10.15252/embj.201592188. Epub 2015 Sep 4.
Diversification of neuron classes is essential for functions of the olfactory system, but the underlying mechanisms that generate individual olfactory neuron types are only beginning to be understood. Here we describe a role of the highly conserved HMG-box transcription factor SOX-2 in postmitotic specification and alternative differentiation of the Caenorhabditis elegans AWC and AWB olfactory neurons. We show that SOX-2 partners with different transcription factors to diversify postmitotic olfactory cell types. SOX-2 functions cooperatively with the OTX/OTD transcription factor CEH-36 to specify an AWC "ground state," and functions with the LIM homeodomain factor LIM-4 to suppress this ground state and drive an AWB identity instead. Our findings provide novel insights into combinatorial codes that drive terminal differentiation programs in the nervous system and reveal a biological function of the deeply conserved Sox2 protein that goes beyond its well-known role in stem cell biology.
神经元类别的多样化对于嗅觉系统的功能至关重要,但产生个体嗅觉神经元类型的潜在机制才刚刚开始被理解。在这里,我们描述了高度保守的HMG盒转录因子SOX-2在秀丽隐杆线虫AWC和AWB嗅觉神经元的有丝分裂后特化和交替分化中的作用。我们表明,SOX-2与不同的转录因子合作,使有丝分裂后的嗅觉细胞类型多样化。SOX-2与OTX/OTD转录因子CEH-36协同作用,以确定AWC的“基态”,并与LIM同源域因子LIM-4共同作用,抑制该基态并驱动AWB身份。我们的发现为驱动神经系统终末分化程序的组合密码提供了新的见解,并揭示了深度保守的Sox2蛋白的生物学功能,该功能超出了其在干细胞生物学中众所周知的作用。