scholarly journals Developmental Toxicity Assessment of Piperonyl Butoxide Exposure Targeting Sonic Hedgehog Signaling and Forebrain and Face Morphogenesis in the Mouse: An in Vitro and in Vivo Study

2019 ◽  
Vol 127 (10) ◽  
pp. 107006 ◽  
Author(s):  
Joshua L. Everson ◽  
Miranda R. Sun ◽  
Dustin M. Fink ◽  
Galen W. Heyne ◽  
Cal G. Melberg ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Developmental Toxicity ◽  
Toxicity Assessment ◽  
Piperonyl Butoxide ◽  
In Vivo Study ◽  
Sonic Hedgehog Signaling

Sonic hedgehog-dependent emergence of oligodendrocytes in the telencephalon: evidence for a source of oligodendrocytes in the olfactory bulb that is independent of PDGFRα signaling

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 4993-5004
Author(s):  
Nathalie Spassky ◽  
Katharina Heydon ◽  
Arnaud Mangatal ◽  
Alexandar Jankovski ◽  
Christelle Olivier ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Olfactory Bulb ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Molecular Mechanisms ◽  
Cell Contact ◽  
Sonic Hedgehog Signaling ◽  
Oligodendrocyte Progenitors

Most studies on the origin of oligodendrocyte lineage have been performed in the spinal cord. By contrast, molecular mechanisms that regulate the appearance of the oligodendroglial lineage in the brain have not yet attracted much attention. We provide evidence for three distinct sources of oligodendrocytes in the mouse telencephalon. In addition to two subpallial ventricular foci, the anterior entopeduncular area and the medial ganglionic eminence, the rostral telencephalon also gives rise to oligodendrocytes. We show that oligodendrocytes in the olfactory bulb are generated within the rostral pallium from ventricular progenitors characterized by the expression of Plp. We provide evidence that these Plp oligodendrocyte progenitors do not depend on signal transduction mediated by platelet-derived growth factor receptors (PDGFRs), and therefore propose that they belong to a different lineage than the PDGFRα-expressing progenitors. Moreover, induction of oligodendrocytes in the telencephalon is dependent on sonic hedgehog signaling, as in the spinal cord. In all these telencephalic ventricular territories, oligodendrocyte progenitors were detected at about the same developmental stage as in the spinal cord. However, both in vivo and in vitro, the differentiation into O4-positive pre-oligodendrocytes was postponed by 4-5 days in the telencephalon in comparison with the spinal cord. This delay between determination and differentiation appears to be intrinsic to telencephalic oligodendrocytes, as it was not shortened by diffusible or cell-cell contact factors present in the spinal cord.

scholarly journals Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Mingxia Wang ◽  
Shangling Zhu ◽  
Weixiang Peng ◽  
Qiuxia Li ◽  
Zhaoxia Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Sonic Hedgehog ◽  
Therapeutic Target ◽  
Hedgehog Signaling ◽  
Specific Inhibitor ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling ◽  
Novel Therapeutic

Sonic hedgehog (Shh) signaling controls many aspects of human development, regulates cell growth and differentiation in adult tissues, and is activated in a number of malignancies. Rheumatoid arthritis (RA) is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS). We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1) in RA synovial tissues was examined by immunohistochemistry (IHC) and in FLS by IHC, immunofluorescence (IF), quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (P<0.05). Cyclopamine (a specific inhibitor of Shh signaling) decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G1phase. Our data show that Shh signaling is activated in synovium of RA patientsin vivoand in cultured FLS form RA patientsin vitro, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA.

scholarly journals Toxicity Assessment of Wild Mushrooms from the Western Ghats, India: An in Vitro and Sub-Acute in Vivo Study

2018 ◽  
Vol 9 ◽  
Author(s):  
S. Sai Latha ◽  
S. Naveen ◽  
C. K. Pradeep ◽  
C. Sivaraj ◽  
M. G. Dinesh ◽  
...  
Keyword(s):  
Western Ghats ◽  
Toxicity Assessment ◽  
In Vivo Study ◽  
Wild Mushrooms ◽  
The Western Ghats

scholarly journals Trisomy 21 induces pericentrosomal crowding disrupting early stages of primary ciliogenesis and mouse cerebellar development

2021 ◽  
Author(s):  
Cayla E Jewett ◽  
Bailey L McCurdy ◽  
Eileen T O'Toole ◽  
Katherine S Given ◽  
Carrie H Lin ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Sonic Hedgehog ◽  
Trisomy 21 ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Chromosome 21 ◽  
Sonic Hedgehog Signaling ◽  
Trafficking Defects ◽  
Microtubule Networks

Primary cilia are signaling organelles essential for development and homeostasis. Loss of primary cilia is lethal, and decreased or defective cilia cause multisystemic conditions called ciliopathies. Down syndrome shares clinical overlap with ciliopathies. We previously showed that trisomy 21 diminishes primary cilia formation and function due to elevated Pericentrin, a centrosome protein encoded on chromosome 21. Pericentrin is mislocalized, creating aggregates that disrupt pericentrosomal trafficking and microtubule organization. Here, we examine the cilia-related molecules and pathways disrupted in trisomy 21 and their in vivo phenotypic relevance. Utilizing ciliogenesis time course experiments, we reveal how Pericentrin, microtubule networks, and components of ciliary vesicles are reorganized for ciliogenesis in euploid cells. Early in ciliogenesis, chromosome 21 polyploidy results in elevated Pericentrin and microtubule networks away from the centrosome that ensnare MyosinVA and EHD1, blocking mother centriole uncapping that is essential for ciliogenesis. Ciliated trisomy 21 cells have persistent trafficking defects that reduce transition zone protein localization, which is critical for Sonic hedgehog signaling. Sonic hedgehog signaling is decreased and anticorrelates with Pericentrin levels in trisomy 21 primary mouse embryonic fibroblasts. Finally, we observe decreased ciliation in vivo. A mouse model of Down syndrome with elevated Pericentrin has fewer primary cilia in cerebellar granule neuron progenitors and thinner external granular layers. Our work reveals that elevated Pericentrin in trisomy 21 disrupts multiple early steps of ciliogenesis and creates persistent trafficking defects in ciliated cells. This pericentrosomal crowding results in signaling defects consistent with the neurological deficits found in individuals with Down syndrome.

FoxF1 is Required for Ciliogenesis and Distribution of Sonic Hedgehog Signaling Components in Cilium

2019 ◽  
Vol 19 (5) ◽  
pp. 326-334
Author(s):  
Lu Huang ◽  
Marco Tjakra ◽  
Desha Luo ◽  
Lin Wen ◽  
Daoxi Lei ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
3T3 Cells ◽  
Shh Signaling ◽  
Nih 3T3 ◽  
Signaling Components ◽  
Nih 3T3 Cells

Background: In vertebrates, cilium is crucial for Hedgehog signaling transduction. Forkhead box transcriptional factor FoxF1 is reported to be associated with Sonic Hedgehog (Shh) signaling in many cases. However, the role of FoxF1 in cilium remains unknown. Here, we showed an essential role of FoxF1 in the regulation of ciliogenesis and in the distribution of Shh signaling components in cilium. Methods: NIH/3T3 cells were serum starved for 24h to induce cilium. Meanwhile, shRNA was used to knockdown the FoxF1 expression in the cells and CRISPR/Cas9 was used to generate the FoxF1 zebrafish mutant. The mRNA and protein expression of indicated genes were detected by the qRT-PCR and western blot, respectively. Immunofluorescence staining was performed to detect the cilium and Shh components distribution. Results: FoxF1 knockdown decreased the cilium length in NIH/3T3 cells. Meanwhile, the disruption of FoxF1 function inhibited the expression of cilium-related genes and caused an abnormal distribution of Shh components in the cilium. Furthermore, homozygous FoxF1 mutants exhibited defective development of pronephric cilium in early zebrafish embryos. Conclusion: Together, our data illustrated that FoxF1 is required for ciliogenesis in vitro and in vivo and for the proper localization of Shh signaling components in cilium.

The amount of sonic hedgehog in multiple sclerosis white matter is decreased and cleavage to the signaling peptide is deficient

2003 ◽  
Vol 9 (4) ◽  
pp. 362-371 ◽  
Author(s):  
Fabrizio G Mastronardi ◽  
Luis AG daCruz ◽  
Huimin Wang ◽  
Joan Boggs ◽  
Mario A Moscarello
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Precursor Protein ◽  
Partial Purification ◽  
Sonic Hedgehog Signaling ◽  
Signaling Protein ◽  
Oligodendrocyte Development

We have demonstrated that sonic hedgehog (Shh), vital for oligodendrocyte development, is present in both gray and white matter of normal human brain. Both the 45 kDa precursor protein and the 20 kDa N-terminal sonic hedgehog signaling portion (ShhN) were demonstrated by immunoblot and a partial purification has been achieved. In gray matter from brains of multiple sclerosis (MS) victims, the total amount of Shh was less than normals and the signaling 20 kDa protein was greatly reduced. In white matter homogenates, prepared from MS victims, only the 45 kDa precursor protein was found. None of the 20 kDa signaling protein was detected, suggesting that the 45 kDa signaling protein was not cleaved in the autocatalytic reaction carried out by the C -terminal portion. The 45 kDa protein and a small amount of the 20 kDa ShhN was detected in isolated MS myelin by Western blot, demonstrating some cleavage was possible. The cleavage of the 45 kDa protein was demonstrated in normal myelin in vitro, but not in myelin prepared from MS brain.

Platelet-derived growth factor-A and sonic hedgehog signaling direct lung fibroblast precursors during alveolar septal formation

2013 ◽  
Vol 305 (3) ◽  
pp. L229-L239 ◽  
Author(s):  
Stephen E. McGowan ◽  
Diann M. McCoy
Keyword(s):  
Growth Factor ◽  
Gas Exchange ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Platelet Derived Growth Factor ◽  
Lung Fibroblasts ◽  
Alveolar Cells ◽  
Sonic Hedgehog Signaling

Alveolar septal formation is required to support the respiration of growing mammals; in humans effacement of the alveolar surface and impaired gas exchange are critical features of emphysema and pulmonary fibrosis. Platelet-derived growth factor-A (PDGF-A) and its receptor PDGF-receptor-α (PDGFRα) are required for secondary septal elongation in mice during postnatal days 4 through 12 and they regulate the proliferation and septal location of interstitial fibroblasts. We examined lung fibroblasts (LF) to learn whether PDGFRα expression distinguished a population of precursor cells, with enhanced proliferative and migratory capabilities. We identified a subpopulation of LF that expresses sonic hedgehog (Shh) and stem cell antigen-1 (Sca1). PDGF-A and Shh both increased cytokinesis and chemotaxis in vitro, but through different mechanisms. In primary LF cultures, Shh signaled exclusively through a noncanonical pathway involving generation of Rac1-GTP, whereas both the canonical and noncanonical pathways were used by the Mlg neonatal mouse LF cell line. LF preferentially oriented their primary cilia toward their anterior pole during migration. Furthermore, a larger proportion of PDGFRα-expressing LF, which are more abundant at the septal tips, bore primary cilia compared with other alveolar cells. In pulmonary emphysema, destroyed alveolar septa do not regenerate, in part because cells fail to assume a configuration that allows efficient gas exchange. Better understanding how LF are positioned during alveolar development could identify signaling pathways, which promote alveolar septal regeneration.

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