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https://www.readbyqxmd.com/read/29679559/foxd1-is-required-for-terminal-differentiation-of-anterior-hypothalamic-neuronal-subtypes
#1
Elizabeth A Newman, Dong Won Kim, Jun Wan, Jie Wang, Jiang Qian, Seth Blackshaw
Although the hypothalamus functions as a master homeostat for many behaviors, little is known about the transcriptional networks that control its development. To investigate this question, we analyzed mice deficient for the Forkhead domain transcription factor Foxd1. Foxd1 is selectively expressed in neuroepithelial cells of the prethalamus and hypothalamus prior to the onset of neurogenesis, and is later restricted to neural progenitors of the prethalamus and anterior hypothalamus. During early stages of neurogenesis, we observed that Foxd1-deficient mice showed reduced expression of Six3 and Vax1 in anterior hypothalamus, but overall patterning of the prethalamus and hypothalamus is unaffected...
April 18, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29667914/inactivation-of-map3k7-in-foxd1-expressing-cells-results-in-loss-of-mesangial-pdgfr%C3%AE-and-juvenile-kidney-scarring
#2
Michele J Karolak, Justin A Guay, Leif Oxburgh
Transforming growth factor beta (TGFβ) plays a central role in renal scarring, controlling extracellular matrix deposition by interstitial cells and mesangial cells. TGFβ signals through Smad and mitogen activated protein kinase (MAPK) pathways. To understand the role of MAPK in interstitial and mesangial cells, we genetically inactivated TGFβ-activated kinase 1 (Map3k7) using Foxd1+/cre. Embryonic kidney development was unperturbed in mutants, but spontaneous scarring of the kidney ensued during the first postnatal week, with retention of embryonic nephrogenic rests and accumulation of collagen IV in the mesangium...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29620165/foxd1-is-targeted-by-mir-30a-5p-and-mir-200a-5p-and-suppresses-the-proliferation-of-human-ovarian-carcinoma-cells-by-promoting-p21-expression-in-a-p53-independent-manner
#3
Yu Wang, Chunping Qiu, Nan Lu, Zhaojian Liu, Chengjuan Jin, Chenggong Sun, Hualei Bu, Hongfeng Yu, Samina Dongol, Beihua Kong
High-grade serous ovarian carcinoma (HGSOC) accounts for the highest number of deaths among patients with epithelial ovarian cancer. However, the molecular mechanisms underlying HGSOC tumorigenesis are currently unclear. In the present study, a lentiviral expression system was employed to manipulate forkhead box D1 (FOXD1) expression in ovarian cancer cells. Immunohistochemical staining was used to examine the expression of FOXD1 in tissue samples. Clonogenic and MTT assays were employed to evaluate cell proliferation, and flow cytometry was applied for cell cycle analysis...
April 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29449449/conserved-and-divergent-features-of-mesenchymal-progenitor-cell-types-within-the-cortical-nephrogenic-niche-of-the-human-and-mouse-kidney
#4
Nils O Lindström, Jinjin Guo, Albert D Kim, Tracy Tran, Qiuyu Guo, Guilherme De Sena Brandine, Andrew Ransick, Riana K Parvez, Matthew E Thornton, Laurence Basking, Brendan Grubbs, Jill A McMahon, Andrew D Smith, Andrew P McMahon
Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, and immunolabeling to characterize the presumptive NPC and IPC compartments of the developing human kidney...
March 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29284139/coordinated-d-cyclin-foxd1-activation-drives-mitogenic-activity-of-the-sonic-hedgehog-signaling-pathway
#5
Dustin M Fink, Miranda R Sun, Galen W Heyne, Joshua L Everson, Hannah M Chung, Sookhee Park, Michael D Sheets, Robert J Lipinski
Sonic Hedgehog (Shh) signaling plays key regulatory roles in embryonic development and postnatal homeostasis and repair. Modulation of the Shh pathway is known to cause malformations and malignancies associated with dysregulated tissue growth. However, our understanding of the molecular mechanisms by which Shh regulates cellular proliferation is incomplete. Here, using mouse embryonic fibroblasts, we demonstrate that the Forkhead box gene Foxd1 is transcriptionally regulated by canonical Shh signaling and required for downstream proliferative activity...
April 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29229597/nkx2-2as-suppression-contributes-to-the-pathogenesis-of-sonic-hedgehog-medulloblastoma
#6
Yimeng Zhang, Ting Wang, Shan Wang, Yanlu Xiong, Rui Zhang, Xiang Zhang, Jing Zhao, An-Gang Yang, Lei Wang, Lintao Jia
Aberrant Hedgehog signaling and excessive activation of the Gli family of transcriptional activators are key drivers of medulloblastoma (MB), the most common human pediatric brain malignancy. MB originates mainly from cerebellar granule neuron progenitors (CGNP), but the mechanisms underlying CGNP transformation remain largely obscure. In this study, we found that suppression of the noncoding RNA Nkx2-2as promoted Sonic Hedgehog (Shh)-potentiated MB development. Nkx2-2as functioned as a competing endogenous RNA against miR-103 and miR-107, sequestering them and thereby derepressing their tumor suppressive targets BTG2 and LATS1 and impeding cell division and migration...
February 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29153134/phd-in-the-foxd1-lineage-cells-links-hypoxia-to-inappropriate-nephrogenesis
#7
Tetsuhiro Tanaka
Insufficient oxygenation during pregnancy negatively influences kidney development, which likely serves as a predisposing factor in chronic kidney disease at later stages in life. In this issue of Kidney International, Kobayashi et al. demonstrate that deletion of prolyl hydroxylase 2 and 3, 2 of the major oxygen sensors, in the FoxD1 lineage cells reduces kidney size and inhibits nephrogenesis in mice. Temporospatial expression pattern and studies on additional knockouts suggest the involvement of hypoxia-inducible factor 2...
December 2017: Kidney International
https://www.readbyqxmd.com/read/28892094/deletion-of-pkd1-in-renal-stromal-cells-causes-defects-in-the-renal-stromal-compartment-and-progressive-cystogenesis-in-the-kidney
#8
Xuguang Nie, Lois J Arend
Autosomal dominant polycystic kidney disease (ADPKD), caused by PKD1 and PKD2 gene mutations, is one of the most common genetic diseases, affecting up to 1 in 500 people. Mutations of PKD1 account for over 85% of ADPKD cases. However, mechanisms of disease progression and explanations for the wide range in disease phenotype remain to be elucidated. Moreover, functional roles of PKD1 in the renal stromal compartment are poorly understood. In this work, we tested if Pkd1 is essential for development and maintenance of the renal stromal compartment and if this role contributes to pathogenesis of polycystic kidney disease using a novel tissue-specific knockout mouse model...
December 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28701517/mesangial-cell-mammalian-target-of-rapamycin-complex-1-activation-results-in-mesangial-expansion
#9
Kojiro Nagai, Tatsuya Tominaga, Sayo Ueda, Eriko Shibata, Masanori Tamaki, Motokazu Matsuura, Seiji Kishi, Taichi Murakami, Tatsumi Moriya, Hideharu Abe, Toshio Doi
Human glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)-S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]...
October 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28665931/foxd1-is-an-upstream-regulator-of-the-renin-angiotensin-system-during-metanephric-kidney-development
#10
Renfang Song, Maria Luisa S Sequeira Lopez, Ihor V Yosypiv
BackgroundWe tested the hypothesis that Foxd1, a transcription factor essential for normal kidney development, is an upstream regulator of the renin-angiotensin system (RAS) during ureteric bud (UB)-branching morphogenesis.MethodsUB branching, RAS gene, and protein expression were studied in embryonic mouse kidneys. RAS mRNA expression was studied in mesenchymal MK4 cells.ResultsThe number of UB tips was reduced in Foxd1(-/-) compared with that in Foxd1(+/+) metanephroi on embryonic day E12.5 (14±2.1 vs. 28±1...
November 2017: Pediatric Research
https://www.readbyqxmd.com/read/28651950/the-loss-of-kr%C3%A3-ppel-like-factor-15-in-foxd1-stromal-cells-exacerbates-kidney-fibrosis
#11
Xiangchen Gu, Sandeep K Mallipattu, Yiqing Guo, Monica P Revelo, Jesse Pace, Timothy Miller, Xiang Gao, Mukesh K Jain, Agnieszka B Bialkowska, Vincent W Yang, John C He, Changlin Mei
Large epidemiological studies clearly demonstrate that multiple episodes of acute kidney injury contribute to the development and progression of kidney fibrosis. Although our understanding of kidney fibrosis has improved in the past two decades, we have limited therapeutic strategies to halt its progression. Myofibroblast differentiation and proliferation remain critical to the progression of kidney fibrosis. Although canonical Wnt signaling can trigger the activation of myofibroblasts in the kidney, mediators of Wnt inhibition in the resident progenitor cells are unclear...
November 2017: Kidney International
https://www.readbyqxmd.com/read/28621426/foxd1-protein-interacts-with-wnt-and-bmp-signaling-to-differentially-pattern-mesoderm-and-neural-tissue
#12
Hanna Polevoy, Anastasia Malyarova, Yuri Fonar, Sara Elias, Dale Frank
The foxd1 gene (previously known as Brain Factor 2/BF2) is expressed during early Xenopus laevis development. At gastrula stages, foxd1 is expressed in dorsal mesoderm regions fated for muscle and notochord, while at neurula stages, foxd1 is expressed in the forebrain region. Previous studies in the neural plate showed that FoxD1 protein acts as transcriptional repressor downstream of BMP antagonism, neuralizing the embryo to control anterior neural cell fates. FoxD1 mesoderm function was not rigorously analyzed, but ectopic FoxD1 levels increased muscle marker expression in embryos...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28539333/endothelial-marker-expressing-stromal-cells-are-critical-for-kidney-formation
#13
Elina Mukherjee, Katherine Maringer, Emily Papke, Daniel Bushnell, Caitlin Schaefer, Rafael Kramann, Jacqueline Ho, Benjamin D Humphreys, Carlton Bates, Sunder Sims-Lucas
Kidneys are highly vascularized and contain many distinct vascular beds. However, the origins of renal endothelial cells and roles of the developing endothelia in the formation of the kidney are unclear. We have shown that the Foxd1-positive renal stroma gives rise to endothelial marker-expressing progenitors that are incorporated within a subset of peritubular capillaries; however, the significance of these cells is unclear. The purpose of this study was to determine whether deletion of Flk1 in the Foxd1 stroma was important for renal development...
September 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28535371/repression-of-interstitial-identity-in-nephron-progenitor-cells-by-pax2-establishes-the-nephron-interstitium-boundary-during-kidney-development
#14
Natalie Naiman, Kaoru Fujioka, Mari Fujino, M Todd Valerius, S Steven Potter, Andrew P McMahon, Akio Kobayashi
The kidney contains the functional units, the nephrons, surrounded by the renal interstitium. Previously we discovered that, once Six2-expressing nephron progenitor cells and Foxd1-expressing renal interstitial progenitor cells form at the onset of kidney development, descendant cells from these populations contribute exclusively to the main body of nephrons and renal interstitial tissues, respectively, indicating a lineage boundary between the nephron and renal interstitial compartments. Currently it is unclear how lineages are regulated during kidney organogenesis...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535367/pax2-a-keep-to-the-path-sign-on-waddington-s-epigenetic-landscape
#15
COMMENT
Jamie Davies
Developing kidneys have Foxd1+ stromogenic stem cells and [Six2+ , Pax2+ ] nephrogenic stem cells. In this issue of Developmental Cell, Naiman et al. (2017) show that targeted Pax2 deletion converts nephrogenic cells to the stromogenic path, suggesting that Pax2 normally represses an otherwise inevitable transition between sister lineages.
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28527294/activation-of-hypoxia-signaling-in-stromal-progenitors-impairs-kidney-development
#16
Katharina Gerl, Dominik Steppan, Michaela Fuchs, Charlotte Wagner, Carsten Willam, Armin Kurtz, Birgül Kurt
Intrauterine hypoxia is a reason for impaired kidney development. The cellular and molecular pathways along which hypoxia exerts effects on nephrogenesis are not well understood. They are likely triggered by hypoxia-inducible transcription factors (HIFs), and their effects appear to be dependent on the cell compartment contributing to kidney formation. In this study, we investigated the effects of HIF activation in the developing renal stroma, which also essentially modulates nephron development from the metanephric mesenchyme...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28439006/murine-model-indicates-22q11-2-signaling-adaptor-crkl-is-a-dosage-sensitive-regulator-of-genitourinary-development
#17
Meade Haller, Qianxing Mo, Akira Imamoto, Dolores J Lamb
The spectrum of congenital anomalies affecting either the upper tract (kidneys and ureters) or lower tract (reproductive organs) of the genitourinary (GU) system are fundamentally linked by the developmental origin of multiple GU tissues, including the kidneys, gonads, and reproductive ductal systems: the intermediate mesoderm. Although ∼31% of DiGeorge/del22q11.2 syndrome patients exhibit GU defects, little focus has been placed on the molecular etiology of GU defects in this syndrome. Among del22q11.2 patients exhibiting GU anomalies, we have mapped the smallest relevant region to only five genes, including CRKLCRKL encodes a src-homology adaptor protein implicated in mediating tyrosine kinase signaling, and is expressed in the developing GU-tract in mice and humans...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28286175/cilia-dependent-gli-processing-in-neural-crest-cells-is-required-for-tongue-development
#18
Grethel Millington, Kelsey H Elliott, Ya-Ting Chang, Ching-Fang Chang, Andrzej Dlugosz, Samantha A Brugmann
Ciliopathies are a class of diseases caused by the loss of a ubiquitous, microtubule-based organelle called a primary cilium. Ciliopathies commonly result in defective development of the craniofacial complex, causing midfacial defects, craniosynostosis, micrognathia and aglossia. Herein, we explored how the conditional loss of primary cilia on neural crest cells (Kif3a(f/f);Wnt1-Cre) generated aglossia. On a cellular level, our data revealed that aglossia in Kif3a(f/f);Wnt1-Cre embryos was due to a loss of mesoderm-derived muscle precursors migrating into and surviving in the tongue anlage...
April 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28075458/silencing-of-forkhead-box-d1-inhibits-proliferation-and-migration-in-glioma-cells
#19
Yuan-Feng Gao, Tao Zhu, Xiao-Yuan Mao, Chen-Xue Mao, Ling Li, Ji-Ye Yin, Hong-Hao Zhou, Zhao-Qian Liu
Despite the extensive role of Forkhead box transcription factors in the development and progression of various cancers, little is known about their role in glioma. We examined the expression and function of Forkhead box D1 (FOXD1) in glioma cell behavior and found that FOXD1 was upregulated and directly correlated with the glioma grade. Data analysis also revealed significant differences in FOXD1 expression for both gene expression profiles (GSE4290 and GSE7696) and the TCGA datasets. Additionally, decreased FOXD1 expression in U251 and U87 glioma cells caused a delay in cell growth and a disruption in colony formation...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27805902/association-of-foxd1-variants-with-adverse-pregnancy-outcomes-in-mice-and-humans
#20
Paul Laissue, Besma Lakhal, Magalie Vatin, Frank Batista, Gaëtan Burgio, Eric Mercier, Esther Dos Santos, Christophe Buffat, Diana Carolina Sierra-Diaz, Gilles Renault, Xavier Montagutelli, Jane Salmon, Philippe Monget, Reiner A Veitia, Céline Méhats, Marc Fellous, Jean-Christophe Gris, Julie Cocquet, Daniel Vaiman
Recurrent spontaneous abortion (RSA) is a common cause of infertility, but previous attempts at identifying RSA causative genes have been relatively unsuccessful. Such failure to describe RSA aetiological genes might be explained by the fact that reproductive phenotypes should be considered as quantitative traits resulting from the intricate interaction of numerous genetic, epigenetic and environmental factors. Here, we studied an interspecific recombinant congenic strain (IRCS) of Mus musculus from the C57BL6/J strain of mice harbouring an approximate 5 Mb DNA fragment from chromosome 13 from Mus spretus mice (66H-MMU13 strain), with a high rate of embryonic resorption (ER)...
October 2016: Open Biology
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