Expression of Sox8, Sox9 and Sox10 in the developing valves and autonomic nerves of the embryonic heart

Montero, Juan A.; Giron, B; Arrechedera, Héctor; Cheng, Yi-Chuan; Scotting, Paul J.; Chimal‐Monroy, Jesús; García‐Porrero, Juan A.; Hurlé, Juan M.

doi:10.1016/s0925-4773(02)00249-6

Cited by 54 publications

(41 citation statements)

References 22 publications

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“…A branching, twig-like pattern of ␤Gal staining was observed in glial cells that accompanied the progression of peripheral nerves into and over various embryonic organs, including the lungs, heart, bladder, testis, pancreas, arteries, and intestinal tract. Our findings corroborate the recent report of Sox10 expression in the intrinsic ganglia in the lung (Burns and Delalande, 2005) and autonomic nerves of embryonic chick heart (Montero et al, 2002). Visualization of Sox10␤GeoBAC expression in cardiac innervation raises an interesting correlation with the autonomic dysfunction and heart rate variability issues observed in a subset of WS4 patients with a documented Sox10 mutation (Staiano et al, 1999).…”

Section: However the Sox10supporting

confidence: 91%

Distant regulatory elements in a Sox10‐βGEO BAC transgene are required for expression of Sox10 in the enteric nervous system and other neural crest‐derived tissues

Deal

Cantrell

Chandler

et al. 2006

Developmental Dynamics

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Sox10 is an essential transcription factor required for development of neural crest-derived melanocytes, peripheral glia, and enteric ganglia. Multiple transcriptional targets regulated by Sox10 have been identified; however, little is known regarding regulation of Sox10. High sequence conservation surrounding 5 exons 1 through 3 suggests these regions might contain functional regulatory elements. However, we observed that these Sox10 genomic sequences do not confer appropriate cell-specific transcription in vitro when linked to a heterologous reporter. To identify elements required for expression of Sox10 in vivo, we modified bacterial artificial chromosomes (BACs) to generate a Sox10␤GeoBAC transgene. Our approach leaves endogenous Sox10 loci unaltered, circumventing haploinsufficiency issues that arise from gene targeting. Sox10␤GeoBAC expression closely approximates Sox10 expression in vivo, resulting in expression in anterior dorsal neural tube at embryonic day (E) 8.5 and in cranial ganglia, otic vesicle, and developing dorsal root ganglia at E10.5. Characterization of Sox10␤GeoBAC expression confirms the presence of essential regulatory regions and additionally identifies previously unreported expression in thyroid parafollicular cells, thymus, salivary, adrenal, and lacrimal glands. Fortuitous deletions in independent Sox10␤GeoBAC lines result in loss of transgene expression in peripheral nervous system lineages and coincide with evolutionarily conserved regions. Our analysis indicates that Sox10 expression requires the presence of distant cis-acting regulatory elements. The Sox10␤GeoBAC transgene offers one avenue for specifically testing the role of individual conserved regions in regulation of Sox10 and makes possible analysis of Sox10؉ derivatives in the context of normal neural crest development.

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Section: However the Sox10supporting

confidence: 91%

Distant regulatory elements in a Sox10‐βGEO BAC transgene are required for expression of Sox10 in the enteric nervous system and other neural crest‐derived tissues

Deal

Cantrell

Chandler

et al. 2006

Developmental Dynamics

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“…Sox9 belongs to the E subgroup and shares strong homology with Sox8 and Sox10, the other members of this subgroup. In addition, overlapping functions and expressions of these E subgroup genes have been previously described (Montero et al, 2002;Schmidt et al, 2003).…”

Section: Resultsmentioning

confidence: 92%

SOX9 specifies the pyloric sphincter epithelium through mesenchymal-epithelial signals

et al. 2004

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Gastrointestinal (GI) development is highly conserved across vertebrates. Although several transcription factors and morphogenic proteins are involved in the molecular controls of GI development, the interplay between these factors is not fully understood. We report herein the expression pattern of Sox9 during GI development, and provide evidence that it functions,in part, to define the pyloric sphincter epithelium. SOX9 is expressed in the endoderm of the GI tract (with the exclusion of the gizzard) and its derivate organs, the lung and pancreas. Moreover, SOX9 is also expressed at the mesoderm of the pyloric sphincter, a structure that demarcates the gizzard from the duodenum. Using retroviral misexpression technique, we show that Sox9 expression in the pyloric sphincter is under the control of the BMP signaling pathway, known to play a key role in the development of this structure. By misexpressing SOX9 in the mesoderm of the gizzard, we show that SOX9 is able to transdifferentiate the adjacent gizzard epithelium into pyloric sphincter-like epithelium through the control of mesodermal-epithelial signals mediated in part by Gremlin (a modulator of the BMP pathway). Our results suggest that SOX9 is necessary and sufficient to specify the pyloric sphincter epithelial properties.

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“…In the heart valve, several TFs contribute to this role, but how these TFs are coordinated to regulate valve formation is not known. SOX (SRY-type box) 9, a high mobility group (HMG)-box TF, is highly expressed in the newly formed mesenchyme of the developing heart valves (Montero et al, 2002) and its expression is directly downstream of Notch signalling (Chang et al, 2014). In mouse, SOX9 has an essential role in heart valve development (Lincoln et al, 2007): loss of SOX9 in early valve formation leads to hypoplastic endocardial cushions, reduced proliferation and altered ECM deposition whereas at later stages of valve development, the loss of SOX9 causes abnormal ECM patterning, loss of cartilage-associated proteins, and thickened valves (Lincoln et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

SOX9 modulates the expression of key transcription factors required for heart valve development

et al. 2015

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Heart valve formation initiates when endothelial cells of the heart transform into mesenchyme and populate the cardiac cushions. The transcription factor SOX9 is highly expressed in the cardiac cushion mesenchyme, and is essential for heart valve development. Loss of Sox9 in mouse cardiac cushion mesenchyme alters cell proliferation, embryonic survival, and valve formation. Despite this important role, little is known about how SOX9 regulates heart valve formation or its transcriptional targets. Therefore, we mapped putative SOX9 binding sites by ChIP-Seq in E12.5 heart valves, a stage at which the valve mesenchyme is actively proliferating and initiating differentiation. Embryonic heart valves have been shown to express a high number of genes that are associated with chondrogenesis, including several extracellular matrix proteins and transcription factors that regulate chondrogenesis. Therefore, we compared regions of putative SOX9 DNA binding between E12.5 heart valves and E12.5 limb buds. We identified context-dependent and context-independent SOX9-interacting regions throughout the genome. Analysis of contextindependent SOX9 binding suggests an extensive role for SOX9 across tissues in regulating proliferation-associated genes including key components of the AP-1 complex. Integrative analysis of tissuespecific SOX9-interacting regions and gene expression profiles on Sox9-deficient heart valves demonstrated that SOX9 controls the expression of several transcription factors with previously identified roles in heart valve development, including Twist1, Sox4, Mecom and Pitx2. Together, our data identify SOX9-coordinated transcriptional hierarchies that control cell proliferation and differentiation during valve formation.

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Expression of Sox8, Sox9 and Sox10 in the developing valves and autonomic nerves of the embryonic heart

Cited by 54 publications

References 22 publications

Distant regulatory elements in a Sox10‐βGEO BAC transgene are required for expression of Sox10 in the enteric nervous system and other neural crest‐derived tissues

Distant regulatory elements in a Sox10‐βGEO BAC transgene are required for expression of Sox10 in the enteric nervous system and other neural crest‐derived tissues

SOX9 specifies the pyloric sphincter epithelium through mesenchymal-epithelial signals

SOX9 modulates the expression of key transcription factors required for heart valve development

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