Trends in Neurosciences
Research FocusSOX2 functions in adult neural stem cells
Introduction
The recent explosion of interest in stem cell research and its important clinical implications have brought into focus transcription factors of the SRY-related HMG box (SOX) family [1]. Sox2-null mutant embryos cannot give rise to embryonic or trophectoderm lineages, indicating that Sox2 plays an essential role in early embryo precursor cells and their in vitro stem cell equivalents [2]. Sox2 is expressed in other stem cells and precursor cells during development, including neural stem cells (NSC), and therefore it is likely to be involved in self-renewal and precursor differentiation. In the developing CNS, several studies have shown that all three closely related SoxB1 subfamily members, Sox1, Sox2 and Sox3, which are coexpressed in the neuroepithelium [3], function to maintain broad developmental potential and NSC identity 2, 4, 5, 6, 7. Sox1-null [8] and Sox3-null [9] mutant mice are viable and without general CNS defects, suggesting functional redundancy within the subfamily. These facts have prevented elucidation of the role of SOXB1 factors in NSC. However, a recent study by Ferri et al. [10] has established that Sox2 is expressed in adult NSC, and provides genetic evidence that it is involved in their maintenance and/or proliferation.
Section snippets
SOX2 functions in the adult brain
Neurogenesis continues in the adult brain in two germinal layers: the subventricular zone (SVZ) of the lateral ventricle, which provides neuronal precursors that migrate to the olfactory bulb via the rostral migratory stream throughout adult life, and the dentate gyrus subgranular zone of the hippocampus. Cells with structural and molecular characteristics of astrocytes (e.g. expressing glial fibrillary acidic protein, GFAP) are believed to function as neurogenic stem cells in these regions [11]
Molecular mechanism of SOXB1 function in neurogenesis
Proneural transcription factors drive neurogenesis by directing the exit of neural progenitors from the cell cycle and by mediating the expression of genes characteristic of post-mitotic neurons [15]. Bylund et al. [5] and Graham et al. [6] showed that inhibition of SOX2 using dominant-negative constructs promotes premature differentiation of precursors (i.e. exit from cell cycle, loss of progenitor markers and acquisition of early neuronal markers). They also proposed that SOXB1 factors can
Concluding remarks
Before we can really begin to understand the transcriptional networks operating in stem cell maintenance, proliferation and fate commitment, many experiments will be required to identify the specific cofactors, target genes and regulatory pathways of SOXB1 factors. However, the results discussed here highlight the importance of SOX2 in neural development and homeostasis of the adult CNS. Because SOX2 is expressed in other stem cells and developing systems during embryogenesis, more functions
Acknowledgements
I thank Robin Lovell-Badge (NIMR, London) for his advice in the preparation of this review. My laboratory is supported by the Medical Research Council.
References (19)
- et al.
Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre- gastrulation to early somite stages
Mech. Dev.
(1999) - et al.
Sox genes find their feet
Curr. Opin. Genet. Dev.
(1997) SOX2 functions to maintain neural progenitor identity
Neuron
(2003)SoxB transcription factors specify neuroectodermal lineage choice in ES cells
Mol. Cell. Neurosci.
(2004)Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability
Neuroscience
(2003)- et al.
Matching SOX: partner proteins and co-factors of the SOX family of transcriptional regulators
Curr. Opin. Genet. Dev.
(2002) Sox1 acts through multiple independent pathways to promote neurogenesis
Dev. Biol.
(2004)Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain
Development
(2004)A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes
Nature
(1990)
Cited by (198)
Isolation and characterization of neural stem cells from fetal canine spinal cord
2021, Neuroscience LettersSOX2 protein transduction directly converts human fibroblasts into oligodendrocyte-like cells
2020, Biochemical and Biophysical Research CommunicationsDifferential effects of oxytocin on olfactory, hippocampal and hypothalamic neurogenesis in adult sheep
2019, Neuroscience LettersProteolysis of methylated SOX2 protein is regulated by L3MBTL3 and CRL4<sup>DCAF5</sup> ubiquitin ligase
2019, Journal of Biological Chemistry