SRY-box containing gene 11 (Sox11) transcription factor is required for neuron survival and neurite growth

Abstract

The transcription factor Sox11 is expressed at high levels in developing sensory neurons and injured adult neurons but little is known about its transcriptional targets and function. In this study we examined the role of Sox11 using Neuro2a neuroblastoma cells and cultured mouse dorsal root ganglia (DRG) neurons. Results show Sox11 has an essential role in regulation of neuron survival and neurite outgrowth in Neuro2a cells and primary sensory neurons. Neuro2a cells increase expression of Sox11 as they differentiate in culture. Following addition of 20μM retinoic acid (RA), a stimulus for differentiation that enhances neurite growth and differentiation, Sox11 level rises. RNAi-mediated knockdown of Sox11 in RA-differentiated Neuro2a cells caused a decrease in neurite growth and an increase in the percent of apoptotic cells. RNA expression analysis showed that Sox11 knockdown modulated the level of mRNAs encoding several genes related to cell survival and death. Further validation in the Neuro2a model showed Sox11 knockdown increased expression of the proapoptotic gene BNIP3 (Bcl2 interacting protein 1 NIP3) decreased expression of the anti-apoptotic gene TANK (TRAF family member-associated NFκB activator). Cultured primary DRG neurons also express Sox11 and treatment with Sox11 siRNA caused a significant decrease in neurite growth and branching and a decrease in mRNA encoding actin-related protein complex 3 (Arpc3), an actin organizing protein that may be involved in axon growth. The percent of apoptotic neurons also increased in cultures of DRG neurons treated with Sox11 siRNA. Similar to Neuro2a cells, a decrease in TANK gene expression occurred, suggesting at least some overlap in Sox11 transcriptional targets in Neuro2a and DRG neurons. These data are consistent with a central role for Sox11 in regulating events that promote neurite growth and neuron survival.

Plasticity of DNA methylation in a nerve injury model of pain

“…As expected, a considerable fraction of genes were induced or suppressed in response to SNL, 2,938 (28.5%) in the present study, including genes such as AFT3, A2m, NGF, SOCS3, SOX11, and STAT3, which are known to show expression changes following nerve injury. [14][15][16][17][18] As has been proposed in the past, 19 we found genes in which promoter methylation was associated with gene downregulation (29 genes). However, a similar number of genes (36) were upregulated when the promoter was hypermethylated.…”

Nuclear expression of sox11 is highly associated with mantle cell lymphoma but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms

“…8,[16][17][18] However, the data on the roles of SOX genes in hematopoiesis are very limited. To date, SOX4 is the only gene in the family that has been found to have a key role in lymphopoiesis.…”

“…16 Therefore, it is logical to hypothesize that sox11 may contribute to the pathogenesis and/or progression of mantle cell lymphoma and hairy cell leukemia by regulating genes involved in cell proliferation and apoptosis. 26 The mechanism underlying the frequent upregulation of cyclin D1 in hairy cell leukemia is largely unknown.…”

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

“…The transcription factor Sox11 is known to be expressed during later stages of neural development in areas of the brain in which neurons undergo differentiation (Kuhlbrodt et al 1998). In vitro studies suggest that Sox11 is centrally involved in regulating events that promote neurite growth and neuron survival (Jankowski et al 2006). In the adult brain, Sox11 expression is weak under basal conditions but has been found to be up-regulated after experimentally induced seizures or nerve injury and has been linked to injuryinduced neuritogenesis (Elliott et al 2003;Tanabe et al 2003).…”