Archer TC et al. (2011), Interaction of Sox1, Sox2, Sox3 and Oct4 during...

XB-ART-42479

Dev Biol 2011 Feb 15;3502:429-40. doi: 10.1016/j.ydbio.2010.12.013.

Show Gene links Show Anatomy links

Interaction of Sox1, Sox2, Sox3 and Oct4 during primary neurogenesis.

Archer TC , Jin J , Casey ES .

???displayArticle.abstract???
Sox1, Sox2 and Sox3, the three members of the SoxB1 subgroup of transcription factors, have similar sequences, expression patterns and overexpression phenotypes. Thus, it has been suggested that they have redundant roles in the maintenance of neural stem cells in development. However, the long-term effect of overexpression or their function in combination with their putative co-factor Oct4 has not been tested. Here, we show that overexpression of sox1, sox2, sox3 or oct91, the Xenopus homologue of Oct4, results in the same phenotype: an expanded neural plate at the expense of epidermis and delayed neurogenesis. However, each of these proteins induced a unique profile of neural markers and the combination of Oct91 with each SoxB1 protein had different effects, as did continuous misexpression of the proteins. Overexpression studies indicate that Oct91 preferentially cooperates with Sox2 to maintain neural progenitor marker expression, while knockdown of Oct91 inhibits neural induction driven by either Sox2 or Sox3. Continuous expression of Sox1 and Sox2 in transgenic embryos represses neuron differentiation and inhibits anterior development while increasing cell proliferation. Constitutively active Sox3, however, leads to increased apoptosis suggesting that it functions as a tumor suppressor. While the SoxB1s have overlapping functions, they are not strictly redundant as they induce different sets of genes and are likely to partner with different proteins to maintain progenitor identity.

???displayArticle.pubmedLink??? 21147085
???displayArticle.pmcLink??? PMC3033231
???displayArticle.link??? Dev Biol
???displayArticle.grants??? [+]

Species referenced: Xenopus laevis
Genes referenced: pou5f3 sox1 sox2 sox3 tub tubb2b
GO keywords: neurogenesis
???displayArticle.morpholinos??? pou5f3.1 MO1

???attribute.lit??? ???displayArticles.show???

	Fig. 1. Oct91 and Sox1 expand the neural tube and repress epidermal formation similarly to Sox2 and 3. (A) Bright field and fluorescent microscopy of stage 17 embryos injected with Sox1, Sox2, Sox3 or Oct91 and GFP mRNA into one cell of a two- cell stage embryo. (E) WISH for epi-k expression in embryos injected with soxB1 and LacZ, or oct91 and GFP mRNA. Asterisk in E marks the injected side. The injected sides of Sox1 (180/190), Sox2 (135/152), Sox3 (81/81) and Oct91 (49/53) have repressed epi-k expression compared to their uninjected side. All views are dorsal with anterior to the left. Brackets in A compare the relative width of the neural tube of the uninjected (top) to the injected side (bottom)
	Fig. 2. Oct91 and the SoxB1s synergize to induce posterior protrusions. (A) WISH for n-tub in embryos injected in one blastomere of the four-cell stage embryo with LacZ and oct91, sox1, sox2, or sox3 mRNA. Arrowhead in B marks laterally displaced neurons. Ectopic neurons are seen at both stages 23 and 30 in all treatments. (M) WISH for n-tub in embryos injected in one ventral blastomere of a four-cell embryo with oct91 alone or in combination with sox1, sox2 or sox3, and LacZ. Asterisk in top row marks the injected side. In A and M the injected side is the bottom half of the embryo. In I and S only the injected side is shown.
	Fig. 7. A constitutively-active bicistronic vector generates two proteins from a single transcript in Xenopus. (A) A diagram for the bicistronic 2A vector shows that a single transcript forms two proteins. mCherry (pink) contains a plasma membrane localization signal (PmLS, white) and GFP contains nuclear localization signal (NLS, black). (B) Xenopus embryonic fibroblast cell transfected with the bicistronic system with vector in A. mCherry is in the plasma membrane (C) and GFP in the nucleus (D). (F) In vitro transcribed 2A vector mRNA injected into half of the two-cell stage embryo is visible under a dissecting fluorescent microscope in a neurula stage 17 embryo. (I) Bicistronic constructs used for the generation of transgenic embryos. Each SoxB1 (purple) is upstream of the 18 amino acid 2A viral sequence (blue) followed by nuclear localizing GFP (green) and poly-A signal (brown) and expression is controlled by the constitutively-active EFlα promoter (orange). Asterisk marks injected side. Diagram not to scale.
	Fig. 8. Sox1:2A:GFP and Sox2:2A:GFP transgenic embryos have decreased levels of n-tub and Sox2:2A:GFP have increased proliferation. (A) WISH for n-tub. (A) A stage 30 sibling embryo generated from sperm nuclei transfer serves as a staging control. N-tub levels are reduced in the brain and spinal cord of transgenic embryos. (B) Sox1:2A:GFP and (C) Sox2:2A:GFP transgenic embryos. (D) WISH for sox2 in stage 30 transgenic Sox1:2A:GFP embryos. Sox2 is not expanded in embryos with small heads or absent heads. (G) Immunohistochemistry for phosphorylated histone H3 immunohistochemistry in Sox2:2A:GFP transgenic embryos. Embryos are shown at the same magnification. Hatched box indicates magnified view. (G′′) pH3 positive cells have been counted in the magnified views.

References [+] :

Ambrosetti, Synergistic activation of the fibroblast growth factor 4 enhancer by Sox2 and Oct-3 depends on protein-protein interactions facilitated by a specific spatial arrangement of factor binding sites. 1997, Pubmed