Developmental Signals - Sox

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Introduction

Mouse (E10.5) Sox10 expression[1]

The SRY (480000) and SOX proteins share a DNA-binding domain known as the HMG box, defined by a 79-amino acid region.


All SOX proteins have a single HMG box and bind linear DNA (transcription factor) in a sequence-specific manner, resulting in the bending of DNA through large angles. Bending causes the DNA helix to open for some distance, which may affect binding and interactions of other transcription factors. SOX1, SOX2 (184429), and SOX3 (313430) show the closest homology to SRY. They share maximum homology within the HMG domain and are expressed mainly in the developing nervous system of the mouse (Collignon et al., 1996). These genes share significant homology outside the HMG box also and are highly conserved throughout their evolution.


Sox2 is first expressed in very early (morula, blastocyst) development, and has also been identified as one of the 4 "Yamanaka Factors" required to generate an induced pluripotential stem cell (iPS cell). It also forms a trimeric complex with OCT4, yet another "Yamanaka Factor".


Mammals have 20 different SOX proteins that can be subdivided into 8 groups: A, B1, B2, C, D, E, F, G, H.

Sox Links: Sox transcription factors cartoon | Image 1 - Preimplantation Mouse | Image 2 - Preimplantation Mouse | Image 3 - Preimplantation Mouse | Sox | Induced Stem Cells | Yamanaka Factors


Factor Links: hCG | BMP | Sonic hedgehog | HOX | FGF | Nanog | Nodal | Notch | FOX | PAX | Retinoic acid | SIX | Slit2/Robo1 | Sox | TBX | TGF-beta | VEGF | WNT | Hippo | NGF | Category:Molecular

Some Recent Findings

  • Long-term expandable SOX9+ chondrogenic ectomesenchymal cells from human pluripotent stem cells[2] "Here we report the successful generation and long-term expansion of SOX9-expressing CD271(+)PDGFRα(+)CD73(+) chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1(-)CD271(hi)PDGFRα(lo)CD73(-) neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemented with Nodal/Activin/transforming growth factorβ (TGFβ) inhibitor and fibroblast growth factor (FGF). When "primed" with TGFβ, such cells efficiently formed translucent cartilage particles, which were completely mineralized in 12 weeks in immunocompromized mice." Cartilage Development
  • Just how conserved is vertebrate sex determination?[3] "Sex determination in vertebrate embryos has long been equated with gonadal differentiation into testes or ovaries. This view has been challenged over the years by reports of somatic sexual dimorphisms pre-dating gonadal sex differentiation. ...We illustrate these differences by comparing key sex genes in fishes versus birds and mammals, with emphasis on DM domain genes, the SOX-9AMH pathway in the testis and the FOXL2-Aromatase pathway in the ovary. Such comparisons facilitate the identification of ancient versus derived genes involved in gonadal sex determination. The data indicate that vertebrate sex-determining cascades are not as conserved as once thought."
  • Sox2 is essential for formation of trophectoderm in the preimplantation embryo[4] "In preimplantation mammalian development the transcription factor Sox2 (SRY-related HMG-box gene 2) forms a complex with Oct4 and functions in maintenance of self-renewal of the pluripotent inner cell mass (ICM). ...We conclude that the first essential function of Sox2 in the preimplantation mouse embryo is to facilitate establishment of the trophectoderm lineage. Our findings provide a novel insight into the first differentiation event within the preimplantation embryo, namely the segregation of the ICM and TE lineages."
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Sox Expression

Yu Meng, Alfonso Eirin, Xiang-Yang Zhu, Hui Tang, Pritha Chanana, Amir Lerman, Andre J van Wijnen, Lilach O Lerman Obesity-induced mitochondrial dysfunction in porcine adipose tissue-derived mesenchymal stem cells. J. Cell. Physiol.: 2017; PubMed 29243809

Giovanna Calabrese, Rosario Gulino, Raffaella Giuffrida, Stefano Forte, Elisa Figallo, Claudia Fabbi, Lucia Salvatorelli, Lorenzo Memeo, Massimo Gulisano, Rosalba Parenti In Vivo Evaluation of Biocompatibility and Chondrogenic Potential of a Cell-Free Collagen-Based Scaffold. Front Physiol: 2017, 8;984 PubMed 29238307

Laura P Stabile, Mariya Farooqui, Beatriz Kanterewicz, Shira Abberbock, Brenda F Kurland, Brenda Diergaarde, Jill M Siegfried Preclinical Evidence for Combined Use of Aromatase Inhibitors and NSAIDs as Preventive Agents of Tobacco-Induced Lung Cancer. J Thorac Oncol: 2017; PubMed 29233790

Kesavan Meganathan, Emily M A Lewis, Paul Gontarz, Shaopeng Liu, Edouard G Stanley, Andrew G Elefanty, James E Huettner, Bo Zhang, Kristen L Kroll Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development. Proc. Natl. Acad. Sci. U.S.A.: 2017; PubMed 29229852

Boni A Afouda, Adam T Lynch, Eduardo de Paiva Alves, Stefan Hoppler Genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis. Dev. Biol.: 2017; PubMed 29229250

Early Mouse Expression

Mouse Sox2 expression 01.jpg

Mouse Sox2 expression 02.jpg

Mouse Sox2 expression 03.jpg

Limb Expression

Limb patterning factors 05.jpg

Sox9 expression in E12.5 wild-type mouse embryonic forelimb.[5]

Function

Stem Cells

Sox2

  • one of the 4 "Yamanaka factors" (OCT4, SOX2, KLF4, cMyc) required to make a stem cell.


Links: Stem Cells | Shinya Yamanaka

Genital Development

Sox9

  • regulates sex development.

Cartilage Development

Sox9

  • regulates cartilage development.
  • in chondrogenesis model Sox9 is coexpressed with the gene encoding Col2a1 (type II collagen), the major cartilage matrix protein.
  • up-regulated by fibroblast growth factors (FGFs) in primary chondrocytes.
Links:Cartilage Development

Respiratory Development

Sox2

  • regulates patterning of the anterior foregut into ventral (trachea) and dorsal (esophagus) fates
  • endoderm expression during formation of foregut derivatives
  • declines in regions undergoing lung bud morphogenesis
  • declines in ventral region generating the trachea


Links: Respiratory System Development | StemBook - Specification and patterning of the respiratory system

Rib Development

Mouse E12.5 Sox9 Expression.jpg

Sox9 expression in the Mouse (E12.5) rib primordial.[6]

Neural Development

Sox2 binding sites have been identified in mouse cortical (germinal zone) progenitor cells (this study also identified Pax6 and Lhx2 sites)[7]


Links: Neural System Development | Pax | OMIM Sox2

Hearing Development

Sox2 Lineage tracing of Sox2-expressing progenitor cells in the mouse inner ear reveals a broad contribution to non-sensory tissues and insights into the origin of the organ of Corti[8] "The transcription factor Sox2 is both necessary and sufficient for the generation of sensory regions of the inner ear. ...We find that Sox2-expressing cells in the early otocyst give rise to large numbers of non-sensory structures throughout the inner ear, and that Sox2 only becomes a truly prosensory marker at embryonic day (E)11.5. Our fate map reveals the organ of Corti derives from a central domain on the medial side of the otocyst and shows that a significant amount of the organ of Corti derives from a Sox2-negative population in this region."

Links: Inner Ear Development | Mouse Development | OMIM Sox2

Signaling Pathway

Sox transcription factors cartoon

SOX Developmental Signaling Pathways[9]

OMIM


About OMIM "Online Mendelian Inheritance in Man OMIM is a comprehensive, authoritative, and timely compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries contain copious links to other genetics resources." OMIM



References

  1. Anju Paudyal, Christine Damrau, Victoria L Patterson, Alexander Ermakov, Caroline Formstone, Zuzanna Lalanne, Sara Wells, Xiaowei Lu, Dominic P Norris, Charlotte H Dean, Deborah J Henderson, Jennifer N Murdoch The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear. BMC Dev. Biol.: 2010, 10;87 PubMed 20704721 | BMC Dev Biol.
  2. Katsutsugu Umeda, Hirotsugu Oda, Qing Yan, Nadine Matthias, Jiangang Zhao, Brian R Davis, Naoki Nakayama Long-Term Expandable SOX9(+) Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells. Stem Cell Reports: 2015; PubMed 25818812
  3. Andrew Cutting, Justin Chue, Craig A Smith Just how conserved is vertebrate sex determination? Dev. Dyn.: 2013, 242(4);380-7 PubMed 23390004
  4. Maria Keramari, Janet Razavi, Karen A Ingman, Christoph Patsch, Frank Edenhofer, Christopher M Ward, Susan J Kimber Sox2 is essential for formation of trophectoderm in the preimplantation embryo. PLoS ONE: 2010, 5(11);e13952 PubMed 21103067 | PMC2980489 | PLoS One.
  5. Amitabha Bandyopadhyay, Kunikazu Tsuji, Karen Cox, Brian D Harfe, Vicki Rosen, Clifford J Tabin Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet.: 2006, 2(12);e216 PubMed 17194222 | PMC1713256 | PLoS Genet.
  6. Nicholas W Plummer, Karsten Spicher, Jason Malphurs, Haruhiko Akiyama, Joel Abramowitz, Bernd Nürnberg, Lutz Birnbaumer Development of the mammalian axial skeleton requires signaling through the Gα(i) subfamily of heterotrimeric G proteins. Proc. Natl. Acad. Sci. U.S.A.: 2012, 109(52);21366-71 PubMed 23236180 | PMC3535641 | PNAS
  7. Amandine Bery, Yohann Mérot, Sylvie Rétaux Genes expressed in mouse cortical progenitors are enriched in Pax, Lhx, and Sox transcription factor putative binding sites. Brain Res.: 2015; PubMed 26721689
  8. Rende Gu, Rogers M Brown, Chih-Wei Hsu, Tiantian Cai, Alyssa Crowder, Victor G Piazza, Tegy J Vadakkan, Mary E Dickinson, Andrew K Groves Lineage tracing of Sox2(-)expressing progenitor cells in the mouse inner ear reveals a broad contribution to non-sensory tissues and insights into the origin of the organ of Corti. Dev. Biol.: 2016; PubMed 27090805
  9. Kelsie L Thu, Daiana D Becker-Santos, Nikolina Radulovich, Larissa A Pikor, Wan L Lam, Ming-Sound Tsao SOX15 and other SOX family members are important mediators of tumorigenesis in multiple cancer types. Oncoscience: 2014, 1(5);326-35 PubMed 25594027 | Oncoscience

Reviews

Young-Hoon Lee, Jean-Pierre Saint-Jeannet Sox9 function in craniofacial development and disease. Genesis: 2011, 49(4);200-8 PubMed 21309066

Julie C Kiefer Back to basics: Sox genes. Dev. Dyn.: 2007, 236(8);2356-66 PubMed 17584862



Search PubMed: Sox

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Cite this page: Hill, M.A. 2017 Embryology Developmental Signals - Sox. Retrieved December 18, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Sox

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© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G