Abstract
The high-mobility-group (HMG)-domain protein Sox9 is one of few transcription factors implicated in gliogenesis in the vertebrate central nervous system. To further study the role of Sox9 in early spinal cord development, we generated a mouse that allows expression of Sox9 in a temporally and spatially controlled manner. Using this mouse, we show that premature Sox9 expression in neural precursor cells disrupted the neuroepithelium of the ventricular zone. Sox9 also compromised development and survival of neuronal precursors and neurons. Additionally, we observed in these mice substantial increases in oligodendroglial and astroglial cells. Reversing the normal order of appearance of essential transcriptional regulators during oligodendrogenesis, Sox10 preceded Olig2. Our study reinforces the notion that Sox9 has a strong gliogenic activity. It also argues that Sox9 expression has to be tightly controlled to prevent negative effects on early spinal cord structure and neuronal development.
Highlights
In the central nervous system (CNS) gliogenesis follows neurogenesis
Sox9 is one of the few transcriptional regulators that has been associated in the past with commitment to the glial cell lineage in the CNS (Kang et al, 2012; Scott et al, 2010; Stolt et al, 2003)
We have employed an in vivo gain-of-function approach and selectively overexpressed Sox9 in the CNS using an inducible, tetracyclineresponsive tTA-dependent expression system
Summary
In the central nervous system (CNS) gliogenesis follows neurogenesis. Whereas the mechanisms that are responsible for commitment to the neuronal lineage are fairly well studied, much less is known about the corresponding mechanisms for glial commitment. An initial study had shown that in the absence of Sox, glial cells were generated in much fewer numbers in the mouse spinal cord (Stolt et al, 2003). Sox appears to interact with the Notch signaling pathway (Taylor, Yeager, & Morrison, 2007) It induces Nfia as a second gliogenic factor whose temporal expression pattern and interaction with other transcription factors decides over the exact glial fate (Glasgow et al, 2014; Kang et al, 2012). We decided to assess Sox function in the early developing spinal cord by overexpressing the protein from a tetracycline-controlled transgene These studies provide evidence for multiple stage-dependent and cell type-specific functions and show that they are at least in part separable from each other
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