scholarly journals Hedgehog signaling controls dorsoventral patterning, blastema cell proliferation and cartilage induction during axolotl tail regeneration

Development ◽  
2005 ◽  
Vol 132 (14) ◽  
pp. 3243-3253 ◽  
Author(s):  
E. Schnapp
Keyword(s):  
Cell Proliferation ◽  
Hedgehog Signaling ◽  
Dorsoventral Patterning ◽  
Blastema Cell ◽  
Tail Regeneration ◽  
And Cartilage

scholarly journals Perfecting the Imperfect: Introducing dorsoventral patterning into adult regenerating lizard tails with gene-edited embryonic neural stem cells.

2021 ◽  
Author(s):  
Thomas Lozito ◽  
Ricardo Londono ◽  
Aaron Sun ◽  
Megan Hudnall
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Hedgehog Signaling ◽  
Regenerative Process ◽  
Dorsoventral Patterning ◽  
Tail Regeneration ◽  
Neural Tubes ◽  
Roof Plate ◽  
Lepidodactylus Lugubris

Abstract Lizards are able to regrow amputated tails, but the lizard tail regenerative process fails to recapitulate the dorsoventral patterning achieved during embryonic tail development. Regenerated lizard tails form ependymal tubes (ETs) that, like embryonic tail neural tubes (NTs), induce cartilage differentiation in surrounding cells via sonic hedgehog (Shh) signaling. Embryonic NTs are, themselves, dorsoventrally patterned, with Pax7+ Shh- dorsal roof plate domains that restrict cartilage skeletal formation induced by Pax7- Shh+ floor domains to ventral tail regions. However, adult regenerated tail ETs lack characteristically roof plate-associated structures and express Shh throughout their circumferences, resulting in the formation of unpatterned cartilage tube skeletons. Both NTs and ETs contain populations of neural stem cells (NSCs), but only embryonic NSC populations are able to differentiate into roof plate identities and neurons. Embryonic NSCs transplanted into regenerated tail ETs retain the capacity to form roof domains but are ultimately ventralized by the unchecked hedgehog signaling of regenerated lizard tail environments. We hypothesized that only the simultaneous repression of hedgehog signaling and enhancement of NCS roof plate differentiation capacity would induce patterning in lizard ETs and, hence, regenerated cartilage. This was tested through the use of a novel genetic engineering process in which NSCs are isolated from embryos of the parthenogenetic lizard Lepidodactylus lugubris, gene-edited in vivo, and implanted back into clonally-identical adults to regulate tail regeneration. Embryonic lizard NSC lines unresponsive to hedgehog stimulation were generated through the use of CRISPR/Cas9 technologies to knockout (KO) the signaling regulator smoothened (Smo). Exogenous Smo KO NSCs were injected into adult tail spinal cords, where they engrafted to endogenous ependymal cell populations and contributed to dorsal domains in regenerated tail ETs. Embryonic Smo KO NSCs maintained roof plate identities in vivo, and lizards treated with edited NSCs regrew tails that lacked cartilage in dorsal regions. These studies represent an important milestone in the creation of the first regenerated lizard tails with dorsoventrally patterned ETs and skeletal tissues.

scholarly journals Introducing dorsoventral patterning in adult regenerating lizard tails with gene-edited embryonic neural stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Thomas P. Lozito ◽  
Ricardo Londono ◽  
Aaron X. Sun ◽  
Megan L. Hudnall
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Gene Knockout ◽  
Dorsoventral Patterning ◽  
Tail Regeneration ◽  
Neural Tubes ◽  
Cartilage Differentiation ◽  
Roof Plate

AbstractLizards regenerate amputated tails but fail to recapitulate the dorsoventral patterning achieved during embryonic development. Regenerated lizard tails form ependymal tubes (ETs) that, like embryonic tail neural tubes (NTs), induce cartilage differentiation in surrounding cells via sonic hedgehog (Shh) signaling. However, adult ETs lack characteristically roof plate-associated structures and express Shh throughout their circumferences, resulting in the formation of unpatterned cartilage tubes. Both NTs and ETs contain neural stem cells (NSCs), but only embryonic NSC populations differentiate into roof plate identities when protected from endogenous Hedgehog signaling. NSCs were isolated from parthenogenetic lizard embryos, rendered unresponsive to Hedgehog signaling via CRISPR/Cas9 gene knockout of smoothened (Smo), and implanted back into clonally-identical adults to regulate tail regeneration. Here we report that Smo knockout embryonic NSCs oppose cartilage formation when engrafted to adult ETs, representing an important milestone in the creation of regenerated lizard tails with dorsoventrally patterned skeletal tissues.

Dexamethasone induces apoptosis in proliferative canine tendon cells and chondrocytes

2008 ◽  
Vol 21 (04) ◽  
pp. 337-342 ◽  
Author(s):  
M. A. Hossain ◽  
J. Park ◽  
S. H. Choi ◽  
G. Kim
Keyword(s):  
Cell Proliferation ◽  
Cartilage Degeneration ◽  
Dependent Manner ◽  
Tendon Cells ◽  
Cartilage Cells ◽  
In Vitro Effects ◽  
Nuclear Apoptosis ◽  
And Cartilage

SummaryDexamethasone (Dexa) has been commonly used in humans and domestic animals, particularly in the treatment of tendon injuries and cartilage degeneration. However, it is often associated with tendon rupture and impaired tendon and cartilage healing. In the present study, we investigated Dexa’s in vitro effects on the growth of cell proliferation and the induction of apoptosis in canine Achilles tendon cells and chondrocytes. Cell proliferation after treatment with Dexa for two to six days was quantified by a 2,3-bis{2-methoxy- 4-nitro-5-sulfophenyl}-2H-tetrazolium-5-carboxyanilide inner salt assay (XTT). The results showed that Dexa could inhibit the proliferation of tendon cells and chondrocytes at increasing concentrations (0.1–50 μg/ml) compared with untreated cells. Cell apoptosis was induced by Dexa, as evidenced by the typical nuclear apoptosis using Hoechst 33258 staining. Dexa increased the apoptosis of canine tendon cells and chondrocytes in a time-dependent manner. In canine tendon cells and chondrocytes that were treated with 25 and 50 μg/ml concentration of Dexa, the number of condensed apoptotic nuclei was significantly increased. In addition, culturing with Dexa and the glucocorticoid receptor blocker, mifepristone, significantly arrested apoptosis of tendon cells and chondrocytes. Based on our in vitro data, we hypothesized that in vivo treatment with glucocorticoids may diminish the proliferation of tendon and cartilage cells by increasing apoptosis and suppressing the proliferation. Our findings suggest that Dexa could be used with caution in dogs with articular or tendon problems.

scholarly journals Itraconazole inhibits the Hedgehog signaling pathway thereby inducing autophagy-mediated apoptosis of colon cancer cells

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Huiming Deng ◽  
Ling Huang ◽  
Zhongkai Liao ◽  
Mi Liu ◽  
Qiang Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Colon Cancer Cell ◽  
Hedgehog Signaling Pathway ◽  
Colon Cancer Cells ◽  
Hct 116

AbstractItraconazole is as an antifungal medication used to treat systemic fungal infections. Recently, it has been reported to be effective in suppressing tumor growth by inhibiting the Hedgehog signaling pathway and angiogenesis. In the present study, we investigated whether itraconazole induces autophagy-mediated cell death of colon cancer cells through the Hedgehog signaling pathway. Cell apoptosis and cell cycle distribution of the colon cancer cell lines SW-480 and HCT-116 were detected by flow cytometry and terminal TUNEL assay. Autophagy and signal proteins were detected by western blotting and cell proliferation-associated antigen Ki-67 was measured using immunohistochemistry. The images of autophagy flux and formation of autophagosomes were observed by laser scanning confocal and/or transmission electron microscopy. Colon cancer cell xenograft mouse models were also established. Itraconazole treatment inhibited cell proliferation via G1 cell cycle arrest as well as autophagy-mediated apoptosis of SW-480 and HCT-116 colon cancer cells. In addition, the Hedgehog pathway was found to be involved in activation of itraconazole-mediated autophagy. After using the Hedgehog agonist recombinant human Sonic Hedgehog (rhshh), itraconazole could counteract the activation of rhshh. Moreover, treatment with itraconazole produced significant cancer inhibition in HCT-116-bearing mice. Thus, itraconazole may be a potential and effective therapy for the treatment of colon cancer.

Hedgehog Signaling and Maintenance of Homeostasis in the Intestinal Epithelium

Physiology ◽  
2012 ◽  
Vol 27 (3) ◽  
pp. 148-155 ◽  
Author(s):  
Nikè V. J. A. Büller ◽  
Sanne L. Rosekrans ◽  
Jessica Westerlund ◽  
Gijs R. van den Brink
Keyword(s):  
Cell Proliferation ◽  
Negative Feedback ◽  
Intestinal Epithelium ◽  
Hedgehog Signaling ◽  
Dynamic Equilibrium ◽  
Indian Hedgehog ◽  
Feedback Signal ◽  
Epithelial Integrity

Homeostasis of the rapidly renewing intestinal epithelium depends on a balance between cell proliferation and loss. Indian hedgehog (Ihh) acts as a negative feedback signal in this dynamic equilibrium. We discuss recent evidence that Ihh may be one of the key epithelial signals that indicates epithelial integrity to the underlying mesenchyme.

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