The Wilms' Tumor Suppressor Protein WT1 Is Processed by the Serine Protease HtrA2/Omi

Hartkamp, Jörg; Carpenter, Brian; Roberts, Stefan G. E.

doi:10.1016/j.molcel.2009.12.023

Cited by 70 publications

(66 citation statements)

References 35 publications

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“…Continued presence of WT1 in the pre-Sertoli cells promotes the Sertoli cell fate, whereas diminishing Wt1 expression in the interstitial progenitor cells leads to the establishment of interstitial cell lineages. Although how WT1 delineates Sertoli cell fate is not clear, several binding partners of WT1 have been suggested to regulate its activities, such as the transcriptional co-suppressor BASP1 and the serine protease HtrA2 (Carpenter et al, 2004;Hartkamp et al, 2010). Interestingly, Basp1 and Htra2 are expressed at higher levels in pre-Sertoli cells than in interstitial cells at the onset of testis morphogenesis (Jameson et al, 2012).…”

Section: Wt1mentioning

confidence: 99%

Mapping lineage progression of somatic progenitor cells in the mouse fetal testis

2016

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Testis morphogenesis is a highly orchestrated process involving lineage determination of male germ cells and somatic cell types. Although the origin and differentiation of germ cells are known, the developmental course specific for each somatic cell lineage has not been clearly defined. Here, we construct a comprehensive map of somatic cell lineage progression in the mouse testis. Both supporting and interstitial cell lineages arise from WT1 + somatic progenitor pools in the gonadal primordium. A subpopulation of WT1 + progenitor cells acquire SOX9 expression and become Sertoli cells that form testis cords, whereas the remaining WT1 + cells contribute to progenitor cells in the testis interstitium. Interstitial progenitor cells diversify through the acquisition of HES1, an indication of Notch activation, at the onset of sex determination. HES1 + interstitial progenitors, through the action of Sertoli cell-derived Hedgehog signals, become positive for GLI1. The GLI1 + interstitial cells eventually develop into two cell lineages: steroid-producing fetal Leydig cells and non-steroidogenic cells. The fetal Leydig cell population is restricted by Notch2 signaling from the neighboring somatic cells. The non-steroidogenic progenitor cells retain their undifferentiated state during fetal stage and become adult Leydig cells in post-pubertal testis. These results provide the first lineage progression map that illustrates the sequential establishment of somatic cell populations during testis morphogenesis.

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Section: Wt1mentioning

confidence: 99%

Mapping lineage progression of somatic progenitor cells in the mouse fetal testis

2016

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“…ChIP assays were performed as described previously (Hartkamp et al, 2010). Primers for RNA analysis and ChIP analysis are listed in supplementary material Table S1.…”

Section: Rna and Chip Analysismentioning

confidence: 99%

WT1 regulates the development of the posterior taste field

et al. 2014

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Despite the importance of taste in determining nutrient intake, our understanding of the processes that control the development of the peripheral taste system is lacking. Several early regulators of taste development have been identified, including sonic hedgehog, bone morphogenetic protein 4 and multiple members of the Wnt/β-catenin signaling pathway. However, the regulation of these factors, including their induction, remains poorly understood. Here, we identify a crucial role for the Wilms' tumor 1 protein (WT1) in circumvallate (CV) papillae development. WT1 is a transcription factor that is important in the normal development of multiple tissues, including both the olfactory and visual systems. In mice, WT1 expression is detectable by E12.5, when the CV taste placode begins to form. In mice lacking WT1, the CV fails to develop normally and markers of early taste development are dysregulated compared with wild type. We demonstrate that expression of the WT1 target genes Lef1, Ptch1 and Bmp4 is significantly reduced in developing tongue tissue derived from Wt1 knockout mice and that, in normal tongue, WT1 is bound to the promoter regions of these genes. Moreover, siRNA knockdown of WT1 in cultured taste cells leads to a reduction in the expression of Lef1 and Ptch1. Our data identify WT1 as a crucial transcription factor in the development of the CV through the regulation of multiple signaling pathways that have established roles in the formation and patterning of taste placodes.

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“…Previously, the same has been shown for activation of an EMT via expression of Twist [52], so this finding provides another way in which a WT1-controlled EMT could be advantageous for a developing tumour. Finally, WT1 has been implicated in the apoptotic response to cytotoxic stress in chemotherapy through processing by the HtrA2 protease [53,54].…”

Section: Wt1 As An Oncogenementioning

confidence: 99%

WT1 in disease: shifting the epithelial–mesenchymal balance

Miller-Hodges

Hohenstein

2011

The Journal of Pathology

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WT1 is a versatile gene that controls transitions between the mesenchymal and epithelial state of cells in a tissue-context dependent manner. As such, WT1 is indispensable for normal development of many organs and tissues. Uncontrolled epithelial to mesenchymal transition (EMT) is a hallmark of a diverse array of pathologies and disturbance of mesenchymal to epithelial transition (MET) has been associated with a number of developmental abnormalities. It is therefore not surprising that WT1 has been linked to many of these. Here we review the role of WT1 in proper control of the mesenchymal-epithelial balance of cells and discuss how far these roles can explain the role of WT1 in a variety of disease states.

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The Wilms' Tumor Suppressor Protein WT1 Is Processed by the Serine Protease HtrA2/Omi

Cited by 70 publications

References 35 publications

Mapping lineage progression of somatic progenitor cells in the mouse fetal testis

Mapping lineage progression of somatic progenitor cells in the mouse fetal testis

WT1 regulates the development of the posterior taste field

WT1 in disease: shifting the epithelial–mesenchymal balance

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