Abstract
Macrophage migration inhibitory factor (MIF) has important roles in supporting the proliferation and/or survival of murine neural stem/progenitor cells (NSPCs), but downstream effectors remain unknown. We show here that MIF robustly increases the expression of Sox6 in NSPCs in vitro. During neural development, Sox6 is expressed in the ventricular zone of the ganglionic eminence (GE) of mouse brains at embryonic day 14.5 (E14.5), cultured NSPCs from E14.5 GE, and NSPCs in the subventricular zone (SVZ) around the lateral ventricle (LV) of the adult mouse forebrain. Retroviral overexpression of Sox6 in NSPCs increases the number of primary and secondary neurospheres and inhibits cell differentiation. This effect is accompanied with increased expression of Hes1 and Bcl-2 and Akt phosphorylation, thus suggesting a role for Sox6 in promoting cell survival and/or self-renewal ability. Constitutive activation of the transcription factor Stat3 results in up-regulation of Sox6 expression and chromatin immunoprecipitation analysis showed that MIF increases Stat3 binding to the Sox6 promoter in NSPCs, indicating that Stat3 stimulates Sox6 expression downstream of MIF. Finally, the ability of MIF to increase the number of primary and secondary neurospheres is inhibited by Sox6 gene silencing. Collectively, our data identify Sox6 as an important downstream effector of MIF signaling in stemness maintenance of NSPCs.
Highlights
The Sox protein family of transcription factors has been identified as a major group of developmental regulators in vertebrates and invertebrates [1]
migration inhibitory factor (MIF) treatment increased the RNA level of Sox6, but not that of Sox1 and Sox2 (Fig. 1C). These results suggest that the Sox6 gene is a downstream target of MIF signaling in neural/stem progenitor cells (NSPCs)
In the sub-granular zone (SGZ) of the adult mouse hippocampus, Sox6 expression coincided with BrdU labeling expression, indicating that Sox6 was expressed in NSPCs in the adult as it is in the embryo
Summary
The Sox protein family of transcription factors has been identified as a major group of developmental regulators in vertebrates and invertebrates [1]. Sox transcription factors induce or suppress progenitor cell properties, such as proliferation and multipotentiality, or initiate differentiation programs by activating the expression of cell type-specific genes. SoxD proteins harbor two highly conserved functional domains: the family-specific HMG box DNA-binding domain and a groupspecific coiled-coil domain that mediates homodimerization [6]. They have no known transactivation or transrepression domain, but participate in transcriptional activation and repression by utilizing various cofactors to modulate cell proliferation, survival, differentiation, and terminal maturation in a number of mesoderm-, ectoderm-, and endoderm-derived cell lineages [7]. The mechanisms underlying Sox expression and the exact functions of Sox in NSPCs remain underexplored
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
