Interplay of SOX and POU Factors in Regulation of the Nestin Gene in Neural Primordial Cells

Abstract

Intermediate-filament Nestin and group B1 SOX transcription factors (SOX1/2/3) are often employed as markers for neural primordium, suggesting their regulatory link. We have identified adjacent and essential SOX and POU factor binding sites in the Nestin neural enhancer. The 30-bp sequence of the enhancer including these sites (Nes30) showed a nervous system-specific and SOX-POU-dependent enhancer activity in multimeric forms in transfection assays and was utilized in assessing the specificity of the synergism; combinations of either group B1 or group C SOX (SOX11) with class III POU proved effective. In embryonic day 13.5 mouse spinal cord, Nestin was expressed in the cells with nuclei in the ventricular and subventricular zones. SOX1/2/3 expression was confined to the nuclei of the ventricular zone; SOX11 localized to the nuclei of both subventricular (high-level expression) and intermediate (low-level expression) zones. Class III POU (Brn2) was expressed at high levels, localizing to the nucleus in the ventricular and subventricular zones; moderate expression was observed in the intermediate zone, distributed in the cytoplasm. These data support the model that synergic interactions between group B1/C SOX and class III POU within the nucleus determine Nestin expression. Evidence also suggests that such interactions are involved in the regulation of neural primordial cells.

We thank members of the Kondoh laboratory for stimulating discussions and Masato Nakafuku for the provision of MNS70 cells.

This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (12CE2007) and from the Human Frontier Science Program (RGP0040/2001-M) to H.K. and from the National Key Basic Research and Developmental Program (G1999054000 and 2002CB713802) and the National Natural Science Foundation of China (39870283 and 39930090) to N.J.