Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line

Feuerstein, Melanie; Chleilat, Enaam; Khakipoor, Shokoufeh; Michailidis, Konstantinos; Ophoven, Christian; Roussa, Eleni

doi:10.1007/s00441-017-2664-2

Cited by 10 publications

(8 citation statements)

References 60 publications

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“…Our results at E12 are in line with former observations of [8] and [30] at E11.5. A brilliant recent study analyzed the later embryonic stages and described different SHH signalling molecules [31]. In our study we have extended the analysis of dynamic spatiotemporal changes of different SHH signalling molecules investigating their expression along the rostrocaudal axis.…”

Section: Discussionmentioning

confidence: 92%

Spatiotemporal expression of sonic hedgehog signalling molecules in the embryonic mesencephalic dopaminergic neurons of mice

Hussein

Attaai

Kamel

et al. 2021

Preprint

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Background: Midbrain dopaminergic neurons (mDA) play an important role in controlling the voluntary motor movement, reward behaviour and emotion-based behaviour. Differentiation of mDA neurons from progenitors depends on several secreted proteins, such as sonic hedgehog (SHH), and transcription factors. Different groups from mDA neurons arise from the varied patterns of SHH expression during development. The present study attempted to elucidate in mice embryo model, through in situ hybridization and immunohistochemistry 1) the possible role(s) of some SHH signalling components (Ptch1, Gli1, Gli2 and Gli3) in the spatiotemporal development of mDA neurons along the rostrocaudal axis of the midbrain and their possible roles in differentiation (E12, E14) and survival of mDA neurons (E18); 2) the main role of Boc (bioregional Cdon-binding protein), and Gas1 (growth arrest-specific1) as novel accessory receptors for the SHH in the development of mDA neurons 3) the significance of using the primary culture and/or the dopaminergic cell line (MN9D) for studying the development of mDA neurons. Results: At E12 and E14, but not E18, only Ptch1 and Gli1 were expressed in ventrolateral midbrain domains. All examined SHH signalling molecules were not detected in mDA area. Whereas, in MN9D cells, many SHH signalling molecules were expressed and co-localized with the dopaminergic marker; tyrosine hydroxylase (TH), and their expression were upregulated with SHH treatment of the MN9D cells. Conclusion: These results suggest that mDA neurons differentiation and survival are independent of SHH. Besides, MN9D cell line is not the ideal in vitro model for investigating the differentiation of mesencephalic dopaminergic neurons, and hence, the ventral midbrain primary culture might be favored over MN9D line.

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Section: Discussionmentioning

confidence: 92%

Spatiotemporal expression of sonic hedgehog signalling molecules in the embryonic mesencephalic dopaminergic neurons of mice

Hussein

Attaai

Kamel

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Our results at E12 are in line with former observations of [8] and [29] at E11.5. A brilliant recent study analyzed the later embryonic stages and described different SHH signaling molecules [30]. In our study we have extended the analysis of dynamic spatiotemporal changes of different SHH signaling molecules investigating their expression along the rostrocaudal axis.…”

Section: Discussionmentioning

confidence: 92%

Spatiotemporal expression of sonic hedgehog signaling molecules in the embryonic mesencephalic dopaminergic neurons

Hussein

Attaai

Kamel

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background Midbrain dopaminergic neurons (mDA) play an important role in controlling the voluntary motor movement, reward behavior and emotion-based behavior. Differentiation of mDA neurons from progenitors depends on a number of secreted proteins, such as sonic hedgehog (SHH), and transcription factors. Different groups from mDA neurons arise from the varied patterns of SHH expression during development. The present study attempted to elucidate 1) the possible role(s) of some SHH signaling components (Ptch1, Gli1, Gli2 and Gli3) in the spatiotemporal development of mDA neurons along the rostrocaudal axis of the midbrain and their possible roles in differentiation (E12, E14) and survival of mDA neurons (E18); 2) the main role of Boc (bioregional Cdon-binding protein), and Gas1 (growth arrest-specific 1) as novel accessory receptors for the SHH in the development of mDA neurons 3) the significance of using the primary culture and/or the dopaminergic cell line (MN9D) for studying the development of mDA neurons. Results Mice embryos from embryonic day (E)12 were used for in situ hybridization and immunohistochemistry. The primary culture and cell line MN9D were used for in vitro investigation. At E12 and E14, but not E18, only Ptch1 and Gli1 were expressed in ventrolateral midbrain domains. All examined SHH signaling molecules were not detected in mDA area. Whereas, in MN9D cells, many SHH signaling molecules were expressed and co-localized with dopaminergic marker; tyrosine hydroxylase (TH), and their expression were upregulated with SHH treatment of the MN9D cells. Conclusion These results suggest that mDA neurons differentiation and survival are independent of SHH. In addition, MN9D cell line is not the ideal in vitro model for investigating the differentiation of mesencephalic dopaminergic neurons, and hence, the ventral midbrain primary culture might be favored over MN9D line.

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“…First, we verified that SHH activity was elevated in human intrahepatic CCC. Elevated expression of GLI1 and GLI2 is commonly used as a marker for SHH [10,11]. Using publicly available databases, The Cancer Genome Atlas (TCGA), we compared expression levels of GLI1 and GLI2 in intrahepatic CCC with those in non-tumor liver tissues.…”

Section: Activation Of Shh Signaling In Human Intrahepatic CCCmentioning

confidence: 99%

Pharmacological Inhibition of Sonic Hedgehog Signaling Suppresses Tumor Development in a Murine Model of Intrahepatic Cholangiocarcinoma

Cho

Moon

Seo

et al. 2021

IJMS

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Cholangiocarcinoma (CCC) is the second most primary liver cancer with an aggressive biological behavior, and its incidence increases steadily. An aberrant up-regulation of the sonic hedgehog signaling pathway has been reported in a variety of hepatic diseases including hepatic inflammation, fibrosis, as well as cancer. In this study, we determined the effect of a sonic hedgehog inhibitor, vismodegib, on the development of CCC. Through database analyses, we found sonic hedgehog signaling was up-regulated in human CCC, based on overexpression of its target genes, GLI1 and GLI2. Further, human CCC cells were highly sensitive to the treatment with vismodegib in vitro. Based on the data, we investigated the in vivo anti-cancer efficacy of vismodegib in CCC employing a murine model of CCC developed by hydrodynamic tail vein injection method. In the murine model, CCC induced by constitutively active forms of TAZ and PI3K exhibited up-regulated sonic hedgehog signaling. Treatment of vismodegib significantly suppressed tumor development in the murine CCC model, based on comparison of gross morphologies and liver weight/body weight. It is expected that pharmacological inhibition of sonic hedgehog signaling would be an effective molecular target therapy for CCC.

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Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line

Cited by 10 publications

References 60 publications

Spatiotemporal expression of sonic hedgehog signalling molecules in the embryonic mesencephalic dopaminergic neurons of mice

Spatiotemporal expression of sonic hedgehog signalling molecules in the embryonic mesencephalic dopaminergic neurons of mice

Spatiotemporal expression of sonic hedgehog signaling molecules in the embryonic mesencephalic dopaminergic neurons

Pharmacological Inhibition of Sonic Hedgehog Signaling Suppresses Tumor Development in a Murine Model of Intrahepatic Cholangiocarcinoma

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