Understanding the role of SOX9 in acquired diseases: lessons from development

Pritchett, James; Athwal, Varinder; Roberts, Neil; Hanley, Neil A.; Hanley, Karen Piper

doi:10.1016/j.molmed.2010.12.001

Cited by 114 publications

(93 citation statements)

References 94 publications

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“…In addition to proliferation and differentiation, we investigated whether the cystic phenotype resulting from Sox9 perturbations may be a result of abnormal cellular consequences. Studies have shown that Sox9 plays critical roles in both ECM deposition and cell migration in various tissues and diseases (18). In the heart, Sox9 is required for proper organization the valvular ECM proteins (60), whereas in the gonads, Sox9 regulates many ECM proteins as well as modifiers of the ECM such as matrix metalloproteinases (61,62).…”

Section: Discussionmentioning

confidence: 99%

“…However, Sftpc in the early lung marks all distal tip progenitor cells, and recent studies have demonstrated that Sftpc-positive cells in the adult are alveolar stem cells (41). Given that Sftpc can mark progenitor cells, alveolar stem cells, and type 2 differentiated cells, we used surfactant protein B (Sftpb) as a type 2 alveolar cell marker, as it is normally expressed starting at E17.5 (18,42,43). In controls, we observed that Sftpb protein was close to background at E14.5 by immunostaining, whereas Sftpb staining in Sox9 LOF lungs was readily detectable at this time (Fig.…”

Section: Epithelial-specific Loss and Gain Of Sox9 Causes Severe Branmentioning

confidence: 99%

“…Sox9 is a member of the sex-determining region Y (SRY)-related high mobility group (HMG)-box (SOX) transcription factors family that regulates many developmental processes (18). In humans, mutations in SOX9 can lead to several inherited genetic birth defects, including campomelic dysplasia (CD), acampomelic campomelic dysplasia (ACD), Cooks syndrome, and Pierre Robin sequence (or syndrome) (19)(20)(21).…”

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confidence: 99%

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Sox9 plays multiple roles in the lung epithelium during branching morphogenesis

Rockich¹,

Hrycaj

Shih

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

241

249

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Lung branching morphogenesis is a highly orchestrated process that gives rise to the complex network of gas-exchanging units in the adult lung. Intricate regulation of signaling pathways, transcription factors, and epithelial-mesenchymal cross-talk are critical to ensuring branching morphogenesis occurs properly. Here, we describe a role for the transcription factor Sox9 during lung branching morphogenesis. Sox9 is expressed at the distal tips of the branching epithelium in a highly dynamic manner as branching occurs and is down-regulated starting at embryonic day 16.5, concurrent with the onset of terminal differentiation of type 1 and type 2 alveolar cells. Using epithelial-specific genetic loss-and gain-of-function approaches, our results demonstrate that Sox9 controls multiple aspects of lung branching. Fine regulation of Sox9 levels is required to balance proliferation and differentiation of epithelial tip progenitor cells, and loss of Sox9 leads to direct and indirect cellular defects including extracellular matrix defects, cytoskeletal disorganization, and aberrant epithelial movement. Our evidence shows that unlike other endoderm-derived epithelial tissues, such as the intestine, Wnt/β-catenin signaling does not regulate Sox9 expression in the lung. We conclude that Sox9 collectively promotes proper branching morphogenesis by controlling the balance between proliferation and differentiation and regulating the extracellular matrix.organogenesis | campomelic dysplasia

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Section: Discussionmentioning

confidence: 99%

Section: Epithelial-specific Loss and Gain Of Sox9 Causes Severe Branmentioning

confidence: 99%

mentioning

confidence: 99%

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Sox9 plays multiple roles in the lung epithelium during branching morphogenesis

Rockich¹,

Hrycaj

Shih

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

241

249

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“…The SOX family is characterized by a high mobility group (HMG) DNA-binding domain with a high degree of homology to that of SRY (Pritchett et al, 2011). Sox9 belongs to SOX group E (SoxE), along with Sox8 and Sox10 (Foster et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands

et al. 2014

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Murine lacrimal, harderian and meibomian glands develop from the prospective conjunctival and eyelid epithelia and produce secretions that lubricate and protect the ocular surface. Sox9 expression localizes to the presumptive conjunctival epithelium as early as E11.5 and is detected in the lacrimal and harderian glands as they form. Conditional deletion showed that Sox9 is required for the development of the lacrimal and harderian glands and contributes to the formation of the meibomian glands. Sox9 regulates the expression of Sox10 to promote the formation of secretory acinar lobes in the lacrimal gland. Sox9 and FGF signaling were required for the expression of cartilageassociated extracellular matrix components during early stage lacrimal gland development. Fgfr2 deletion in the ocular surface epithelium reduced Sox9 and eliminated Sox10 expression. Sox9 deletion from the ectoderm did not affect Fgf10 expression in the adjacent mesenchyme or Fgfr2 expression in the epithelium, but appeared to reduce FGF signaling. Sox9 heterozygotes showed a haploinsufficient phenotype, in which the exorbital branch of the lacrimal gland was absent in most cases. However, enhancement of epithelial FGF signaling by expression of a constitutively active FGF receptor only partially rescued the lacrimal gland defects in Sox9 heterozygotes, suggesting a crucial role of Sox9, downstream of FGF signaling, in regulating lacrimal gland branching and differentiation.

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“…Recently, this proportion has been revised upwards to include perhaps 40% of cases, based on an observable benefit from pancreatic supplementation; cases of DM have also been noted (Turnpenny and Ellard, 2012). One effector of Notch signaling is SOX9 (Pritchett et al, 2011). The first indication that SOX9 is required for pancreas development and growth came from studies in human embryonic and fetal material, and from post-mortem material in campomelic dysplasia (a skeletal disorder), caused by haploinsufficiency of SOX9 (Piper et al, 2002).…”

Section: Pancreas Agenesis or Hypoplasiamentioning

confidence: 99%

Human pancreas development

et al. 2015

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A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

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Understanding the role of SOX9 in acquired diseases: lessons from development

Cited by 114 publications

References 94 publications

Sox9 plays multiple roles in the lung epithelium during branching morphogenesis

Sox9 plays multiple roles in the lung epithelium during branching morphogenesis

FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands

Human pancreas development

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