The building blocks of mammalian lung development

Rawlins, Emma L.

doi:10.1002/dvdy.22482

Cited by 42 publications

(35 citation statements)

References 111 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…37 Sox2 and Sox9 complementarily cooperate in lung morphogenesis by generating 2 different cell types in the pulmonary system: bronchiole and accessory lobe, respectively. 38 Our findings exclude sequential and complementary modes for Sox7 and Sox17 cooperation because Sox7 and Sox17 were coincidently expressed and lack an epistatic relationship in angiogenic vessels. Sox7 and Sox17 exhibited a substantial overlap in expression, function, and regulation, implying a redundant type of cooperation.…”

Section: Discussionmentioning

confidence: 55%

SoxF Transcription Factors Are Positive Feedback Regulators of VEGF Signaling

Kim

Yang

et al. 2016

Circulation Research

View full text Add to dashboard Cite

Rationale: Vascular endothelial growth factor (VEGF) signaling is a key pathway for angiogenesis and requires highly coordinated regulation. Although the Notch pathway-mediated suppression of excessive VEGF activity via negative feedback is well known, the positive feedback control for augmenting VEGF signaling remains poorly understood. Transcription factor Sox17 is indispensable for angiogenesis, but its association with VEGF signaling is largely unknown. The contribution of other Sox members to angiogenesis also remains to be determined. Objective:

show abstract

Section: Discussionmentioning

confidence: 55%

SoxF Transcription Factors Are Positive Feedback Regulators of VEGF Signaling

Kim

Yang

et al. 2016

Circulation Research

View full text Add to dashboard Cite

show abstract

“…The proximal-distal patterning of the epithelial progenitor cells seems unaffected, as shown by normal distribution of Sox2 + and Sox9 + cells in the E14.5 mutant lungs ( Fig. 2A) (Que et al, 2009;Rawlins, 2011). Similarly, Sox2 expression is maintained in the proximal airways, while Sox9 is lost in the distal lung in both mutants and controls at E18.5 (Fig.…”

Section: ∆/∆mentioning

confidence: 91%

Gpr177 regulates pulmonary vasculature development

Jiang

et al. 2013

Development

View full text Add to dashboard Cite

Establishment of the functional pulmonary vasculature requires intimate interaction between the epithelium and mesenchyme. Previous genetic studies have led to inconsistent conclusions about the contribution of epithelial Wnts to pulmonary vasculature development. This discrepancy is possibly due to the functional redundancy among different Wnts. Here, we use Shh-Cre to conditionally delete Gpr177 (the mouse ortholog of Drosophila Wntless, Wls), a chaperon protein important for the sorting and secretion of Wnt proteins. Deletion of epithelial Gpr177 reduces Wnt signaling activity in both the epithelium and mesenchyme, resulting in severe hemorrhage and abnormal vasculature, accompanied by branching defects and abnormal epithelial differentiation. We then used multiple mouse models to demonstrate that Wnt/β-catenin signaling is not only required for the proliferation and differentiation of mesenchyme, but also is important for the maintenance of smooth muscle cells through the regulation of the transcription factor Kruppel-like factor 2 (Klf2). Together, our studies define a novel mechanism by which epithelial Wnts regulate the normal development and maintenance of pulmonary vasculature. These findings provide insight into the pathobiology of congenital lung diseases, such as alveolar capillary dysplasia (ACD), that have abnormal alveolar development and dysmorphic pulmonary vasculature.

show abstract

“…2A). Because of the dynamic expression of Sox9 in actively branching buds and previous reports demonstrating increased proliferation in distal lung epithelium (2)(3)(4)(5)14), we wanted to determine whether proliferation was affected in Sox9 LOF and Sox9 GOF lungs compared with controls. To quantitate proximal and distal proliferation, control or Sox9 LOF lungs were costained with Sox2 (proximal epithelium), E-cadherin (Ecad; total epithelium), BrdU (proliferation), and DAPI (total nuclei) (SI Appendix, Fig.…”

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

confidence: 99%

“…The distal tips of the domain branches begin to repetitively bifurcate until terminal saccules form at the canalicular stage (E16.5-E17.5). These saccules will eventually give rise to mature alveoli in the adult mouse (2)(3)(4)(5). Several signaling pathways and transcription factors are known to play roles in branching morphogenesis; however, mechanisms controlling morphogenetic movements in the lungs have only recently started to gain attention (1,(6)(7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Sox9 plays multiple roles in the lung epithelium during branching morphogenesis

Rockich¹,

Hrycaj

Shih

et al. 2013

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

243

260

View full text Add to dashboard Cite

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

show abstract

The building blocks of mammalian lung development

Cited by 42 publications

References 111 publications

SoxF Transcription Factors Are Positive Feedback Regulators of VEGF Signaling

SoxF Transcription Factors Are Positive Feedback Regulators of VEGF Signaling

Gpr177 regulates pulmonary vasculature development

Sox9 plays multiple roles in the lung epithelium during branching morphogenesis

Contact Info

Product

Resources

About