WT1 expression in the human fetus during development

Abstract

Wilms’ Tumor 1 (WT1) is a transcription factor involved in the development of the urogenital system. The purpose of this study was to analyze the immunoreactivity for WT1 protein in different tissues and organs in human fetuses in early phases of gestation. To this end, samples from multiple organs were obtained from 4 human fetuses, ranging from 7 up to 12 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained for WT1. Our data show that WT1 is involved in development of multiple human organs in a more vast series of cells types than previously reported. Immunostaining for WT1 was characterized by a predominant cytoplasmic reactivity in the vast majority of cell types. Mesenchimal progenitors in the fetal lung, ductal plate progenitors in fetal liver, cap mesenchimal cells in the developing kidney, fetal zone cells in adrenal glands, atrial and ventricular cardiomyocytes in the fetal heart, radial glial cells in the fetal cerebral cortex and skeletal muscle cell precursors showed the highest levels of WT1 immunoreactivity. Future studies will be needed to detect differences in the expression of WT1 in various organs at different gestational ages, in order to better evaluate the role of WT1 in cell proliferation and differentiation during intrauterine human development.

Interplay of cell–cell contacts and RhoA/ MRTF ‐A signaling regulates cardiomyocyte identity

“…Interestingly, Wt1 expression is restricted only to cells of the epicardium, the outer mesothelial layer of the heart, and completely absent in CMs (Zhou et al , ). Our immunocytochemical and immunohistochemical analyses of human iPSC‐derived CMs and adult human heart tissue indicate that high levels of WT1 are normally detectable in the cytoplasm of human cardiac muscle, confirming previous studies in developing human hearts (Ambu et al , ). Remarkably, we observed a nuclear translocation of WT1 protein occurring during the early phase of cardiomyocyte‐to‐adipocyte conversion in PKP2 and MYH10 mutant cells as well as wt CMs treated with the ROCK inhibitor Y‐27632, suggesting an involvement of cell contact‐mediated RhoA signaling in resolving activation of WT1 as a transcription factor in these cells.…”

Genetic control of cellular morphogenesis in Müller glia

“…Some of these highly conserved genes are known to be involved in glial differentiation. For example, Pax2a (from the Pax2/5/8 family) and the integrins (Itga5, Itga6, and Itgb1a) are expressed in many glial cells, and mutants in all of these genes also resulted in defects in many aspects MG cell morphology (Figure b; Supporting Information Figure S3b–e; Supporting Information Table S4; Supporting Information Figure S3h; Charlton‐Perkins et al, , ; Putaala, Soininen, Kilpeläinen, Wartiovaara, & Tryggvason, ; Quaggin, ; Ambu et al, ; Dzyubenko, Gottschling, & Faissner, ). Remarkably, analysis of the transcriptome of MG cells in pax2a mutants shows that 60% of the genes that affect MG cell morphogenesis in our study have significant changes of expression (Figure c; Supporting Information Table 4).…”

“…Another excellent example of this conserved function is Pax2, which in the eye is primarily known for its function in optic stork formation, and whose expression has been noted in mature MG of chick but not guinea pigs or dogs (Boije, Ring, López‐Gallardo, Prada, & Hallböök, ; Stanke, Moose, El‐Hodiri, & Fischer, ). Pax2 and Wt1 are also crucial for cellular patterning through their regulation of the Nephrins in the brain, kidney, and fly retinal glia (Ambu et al, ; Bao & Cagan, ; Cagan, ; Charlton‐Perkins et al, , ; Flores, Daga, Kalhor, & Banerjee, ; Fu & Noll, ; Putaala et al, ; Quaggin, ; Wagner et al, ). Our transcriptomes indicate that many Nephrins are also temporally enriched in zebrafish MG, they affect glial morphology, and their expression is Pax2a dependent (Supporting Information Table S4).…”

Histochemistry today: Detection and location of single molecules

“…Several papers were aimed at illustrating the tissue organization and protein expression of still poorly described organs from various Vertebrate and Invertebrate species: [42][43][44][45][46][47][48][49][50][51][52][53][54] here, the morphological description of the microanatomical and histological features was paralleled by the detection of specific molecules responsible for the tissue functional characteristics, also as a consequence of seasonal dynamic changes. [55][56][57] The immunolabeling of marker proteins was extensively applied in studies aimed at distinguishing stem/progenitor cells or at elucidating the process of cell differentiation and morphogenesis during pre-and post-natal development in mammals, including humans, [58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76] with special attention to the nervous system, 65,66 sensory organs, [67][68][69] skin, 70 lung, 70,71 and the skeletal apparatus. [72][73][74][75] Also in plants, the histochemical d...…”