SOX18 and the Transcriptional Regulation of Blood Vessel Development

Downes, Meredith; Koopman, Peter

doi:10.1016/s1050-1738(01)00131-1

Cited by 88 publications

(70 citation statements)

References 39 publications

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“…Further, the three SoxF genes are highly expressed in vascular endothelial cells and the developing heart and have important, likely redundant roles in vasculogenesis and cardiogenesis. This conclusion is supported by the effect of dominantnegative Sox18 mutations on the cardiovascular systems of ragged and ragged-like mice Downes and Koopman, 2001;James et al, 2003), by defective cardiogenesis in Xenopus mutants , and by vascular abnormalities in postnatal Sox17/Sox18 double null mice . Sox18, and likely its close relatives, has been shown to mediate its functions in endothelial cells by interacting with the MADS box transcription factor Mef2C and by directly activating the gene for the vascular cell adhesion molecule VCAM1 (Hosking et al, 2001 and2004).…”

Section: Endoderm and Hair Development Cardiogenesis And Angiogenesismentioning

confidence: 86%

Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors

Lefebvre

Dumitriu

Penzo–Méndez

et al. 2007

The International Journal of Biochemistry & Cell Biology

407

358

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Maintain stemness, commit to a specific lineage, differentiate, proliferate, or die. These are essential decisions that every cell is constantly challenged to make in multi-cellular organisms to ensure proper development, adult maintenance, and adaptability. SRY-related high-mobility-group box (Sox) transcription factors have emerged in the animal kingdom to help cells effect such decisions. They are encoded by twenty genes in humans and mice. They share a highly conserved high-mobilitygroup box domain that was originally identified in SRY, the sex-determining gene on the Y chromosome, and that has derived from a canonical high-mobility-group domain characteristic of chromatin-associated proteins. The high-mobility-group box domain binds DNA in the minor groove and increases its DNA binding affinity and specificity by interacting with many types of transcription factors. It also bends DNA and may thereby confer on Sox proteins a unique and critical role in the assembly of transcriptional enhanceosomes. Sox proteins fall into eight groups. Most feature a transactivation or transrepression domain and thereby also act as typical transcription factors. Each gene has distinct expression pattern and molecular properties, often redundant with those in the same group and overlapping with those in other groups. As a whole the Sox family controls cell fate and differentiation in a multitude of processes, such as male differentiation, stemness, neurogenesis, and skeletogenesis. We review their specific molecular properties and in vivo roles, stress recent advances in the field, and suggest directions for future investigations.

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Section: Endoderm and Hair Development Cardiogenesis And Angiogenesismentioning

confidence: 86%

Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors

Lefebvre

Dumitriu

Penzo–Méndez

et al. 2007

The International Journal of Biochemistry & Cell Biology

407

358

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“…It has been suggested that the point mutations found in ragged mice and in dominant forms of human HLT generate a SOX18 protein that acts in a dominant-negative fashion to interfere with the functions of wild-type SOX18 and of related proteins that play a role in vascular, hair follicle or lymphatic development or function, whereas defects in SOX18-null mice are masked by the compensatory action of related SOX factors (James et al, 2003;Downes and Koopman, 2001). In support of this possibility, some evidence has been presented that Sox7, as well as Sox18, is expressed in some populations of developing vascular endothelial cells (Takash et al, 2001;Fawcett and Klymkowsky, 2004).…”

Section: Introductionmentioning

confidence: 99%

Redundant roles ofSox17andSox18in postnatal angiogenesis in mice

Matsui

Kanai‐Azuma

Hara

et al. 2006

Journal of Cell Science

182

168

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Sox7, Sox17 and Sox18 constitute group F of the Sox family of HMG box transcription factor genes. Dominant-negative mutations in Sox18 underlie the cardiovascular defects observed in ragged mutant mice. By contrast, Sox18-/- mice are viable and fertile, and display no appreciable anomaly in their vasculature, suggesting functional compensation by the two other SoxF genes. Here, we provide direct evidence for redundant function of Sox17 and Sox18 in postnatal neovascularization by generating Sox17+/--Sox18-/- double mutant mice. Whereas Sox18-/- and Sox17+/--Sox18+/- mice showed no vascular defects, approximately half of the Sox17+/--Sox18-/- pups died before postnatal day 21 (P21). They showed reduced neovascularization in the liver sinusoids and kidney outer medulla vasa recta at P7, which most likely caused the ischemic necrosis observed by P14 in hepatocytes and renal tubular epithelia. Those that survived to adulthood showed similar, but milder, vascular anomalies in both liver and kidney, and females were infertile with varying degrees of vascular abnormalities in the reproductive organs. These anomalies corresponded with sites of expression of Sox7 and Sox17 in the developing postnatal vasculature. In vitro angiogenesis assays, using primary endothelial cells isolated from the P7 livers, showed that the Sox17+/--Sox18-/- endothelial cells were defective in endothelial sprouting and remodeling of the vasculature in a phenotype-dependent manner. Therefore, our findings indicate that Sox17 and Sox18, and possibly all three SoxF genes, are cooperatively involved in mammalian vascular development.

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“…These findings suggest that the optimal time point for inducible targeted deletion within the DP using the Sox18GCre/ER line is at birth. However, Sox18 is known to be involved in the development of blood and lymphatic vessels, and therefore genetic deletion using the Sox18GCre/ER line may impair other developmental and physiological processes (Downes and Koopman, 2001;Francois et al, 2008). This study confirmed through immunofluorescence that in neonates and at P21, Sox18 (visualised through GFP) colocalised with CD31-and LYVE1-positive cells within the skin, markers of blood and lymphatic vessels, respectively.…”

Section: Discussionsupporting

confidence: 71%

“…Sox18 has been described as an essential regulator of vascular and lymphatic development in the embryo, and is implicated during angiogenesis in skin wound healing (Darby et al, 2001;Downes and Koopman, 2001;Francois et al, 2008). In contrast to Sox2, Sox18 has been described as a DP marker specific to zigzag hair follicles (Driskell et al, 2009;Pennisi et al, 2000a).…”

Section: Sox2 and Sox18 In Dermal Papilla Specificationmentioning

confidence: 99%

Mesenchymal-epidermal interactions in hair follicle cycling and regeneration

Legrand¹

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The hair follicle is an important skin appendage that arises during development from complex reciprocal signalling between the epidermis and dermis. The multiple epidermal layers of the hair follicle are known to be under the control of the mesenchymal component, the dermal papilla (DP), which has been described as the key regulator of hair follicle induction and maintenance. The hair follicle has elicited interest as a model system for the investigation of tissue and organ regeneration due to its ability to regenerate completely throughout the life of a mammal. This characteristic is attributed to the reservoir of stem cells within the hair follicle, which is modulated by the DP.Although it is known that the DP is central to regulation of the hair follicle, mediators of its signalling are incompletely understood. Potential mediators of DP activity continue to emerge, two of which include the SoxF transcription factor, Sox18, and the transcription factor, STAT5. Sox18 has been implicated in hair type specification by the DP; however, its expression and function remains unclear. STAT5 has been shown in microarray analyses of the DP to be specifically expressed and upregulated, while studies involving STAT5 genetic knockouts display a hair phenotype. More recently, STAT5 has been implicated in autoimmune conditions affecting the hair follicle such as alopecia areata.To investigate further the role of STAT5 in the DP, I have hypothesised that STAT5 plays a key role in the DP's hair follicle inductive properties and regulation of cycling.STAT5 activation in the DP was characterised through immunofluorescence staining of mouse back skin at various stages of hair follicle development and cycling. Back skin was obtained from Topflash transgenic mice, a canonical Wnt reporter transgenic mouse driving luciferase expression, using β-catenin activity to monitor hair cycling via live bioluminescence imaging. While embryonic skin did not display any activation of STAT5, during postnatal hair follicle development (P0-P19), the majority of phospho-STAT5 positive DP were present within telogen phase, to a lesser extent within catagen and not at all during anagen. Adult skin showed phospho-STAT5 activation beginning in late catagen and persisting through to early anagen.Characterisation of SOCS2 by immunofluorescence, a downstream STAT5 transcriptional target, showed expression corresponding to the chronology of phospho-STAT5 activity.Hair regeneration assays were performed with DP cells using SKP culture with STAT5 activity modified through adenovirus constructs. SKPs derived from C57BL/6 neonates and STAT5 lox/lox neonates were transduced with STAT5A/B constitutively-active and crerecombinase constructs, respectively. These transduced SKPs were then used in patch assay experiments and DP formation was quantified using a green fluorescent protein ii (GFP) reporter. SKPs transduced with constitutively-active STAT5 were significantly better at forming hair follicle DP than control SKPs transduced with GFP alone. SKPs with...

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SOX18 and the Transcriptional Regulation of Blood Vessel Development

Cited by 88 publications

References 39 publications

Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors

Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors

Redundant roles ofSox17andSox18in postnatal angiogenesis in mice

Mesenchymal-epidermal interactions in hair follicle cycling and regeneration

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