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Conference Paper: Sufu defines the balance of hindbrain progenitor cells maintenance and differentiation

TitleSufu defines the balance of hindbrain progenitor cells maintenance and differentiation
Authors
Issue Date2013
PublisherThe Chinese University of Hong Kong.
Citation
The 2013 Hong Kong Inter-University Biochemistry Postgraduate Symposium, Hong Kong, 15 June 2013. In Symposium Booklet, 2013, abstract T03 How to Cite?
AbstractSuppressor of fused (Sufu) was identified as a regulator in Hedgehog signalling. Study shown that Sufu knockout mice were embryonic lethal at E9.5, exhibiting cephalic deformities, open neural tube and ventralized spinal cord resulting from ectopic Shh signalling, implying indispensable role of Sufu during development of central nervous system. Aiming to investigate the functions of Sufu in hindbrain neurogenesis, we used B2‐r4‐Cre to knock‐out Sufu in rhombomere4 (r4). We observed significant enlargement of mutant r4 size from E10.5, exhibiting more profound expansion in the dorsal region at E12.5. Accordingly, BrdU pulse labelling and sox2 staining showed region specific increased accumulation of proliferative progenitor cells, indicating differential maintenance of progenitor pools along the dorsoventral axis of r4. Tuj1 staining also showed impaired differentiation of the ectopic progenitor cells. Further analysis revealed dramatic dorsal expansion of pMN and p2 progenitor domains in mutant r4. Surprisingly, the FoxA2 positive floor plate, and the dorsal p0 domain were not severely affected, suggesting a novel domain specific regulation of neural progenitor pools by Sufu. Intriguingly, we observed spatial upregulation Gli1 and Gli2 transcription factors, selectively at the region that resides highly proliferative cells, implying that the increased cell proliferation could be caused by the changes of Gli transcription factors. Indeed, concomitant deletion of Gli2 in the Sufu mutant largely rescued the aberrant phenotypes. These findings clearly showed the requirement of Sufu to suppress Gli2 to conduct a domain specific regulation of hindbrain progenitor maintenance and differentiation. Our study demonstrates novel function of Sufu to ensure a tightly controlled progenitor pools maintenance and differentiation, mainly achieve by suppressing Gli2 activation.
Persistent Identifierhttp://hdl.handle.net/10722/184930

 

DC FieldValueLanguage
dc.contributor.authorHor, HHen_US
dc.contributor.authorWang, XAen_US
dc.contributor.authorHui, CCen_US
dc.contributor.authorSham, MHen_US
dc.date.accessioned2013-07-15T10:18:26Z-
dc.date.available2013-07-15T10:18:26Z-
dc.date.issued2013en_US
dc.identifier.citationThe 2013 Hong Kong Inter-University Biochemistry Postgraduate Symposium, Hong Kong, 15 June 2013. In Symposium Booklet, 2013, abstract T03en_US
dc.identifier.urihttp://hdl.handle.net/10722/184930-
dc.description.abstractSuppressor of fused (Sufu) was identified as a regulator in Hedgehog signalling. Study shown that Sufu knockout mice were embryonic lethal at E9.5, exhibiting cephalic deformities, open neural tube and ventralized spinal cord resulting from ectopic Shh signalling, implying indispensable role of Sufu during development of central nervous system. Aiming to investigate the functions of Sufu in hindbrain neurogenesis, we used B2‐r4‐Cre to knock‐out Sufu in rhombomere4 (r4). We observed significant enlargement of mutant r4 size from E10.5, exhibiting more profound expansion in the dorsal region at E12.5. Accordingly, BrdU pulse labelling and sox2 staining showed region specific increased accumulation of proliferative progenitor cells, indicating differential maintenance of progenitor pools along the dorsoventral axis of r4. Tuj1 staining also showed impaired differentiation of the ectopic progenitor cells. Further analysis revealed dramatic dorsal expansion of pMN and p2 progenitor domains in mutant r4. Surprisingly, the FoxA2 positive floor plate, and the dorsal p0 domain were not severely affected, suggesting a novel domain specific regulation of neural progenitor pools by Sufu. Intriguingly, we observed spatial upregulation Gli1 and Gli2 transcription factors, selectively at the region that resides highly proliferative cells, implying that the increased cell proliferation could be caused by the changes of Gli transcription factors. Indeed, concomitant deletion of Gli2 in the Sufu mutant largely rescued the aberrant phenotypes. These findings clearly showed the requirement of Sufu to suppress Gli2 to conduct a domain specific regulation of hindbrain progenitor maintenance and differentiation. Our study demonstrates novel function of Sufu to ensure a tightly controlled progenitor pools maintenance and differentiation, mainly achieve by suppressing Gli2 activation.-
dc.languageengen_US
dc.publisherThe Chinese University of Hong Kong.-
dc.relation.ispartofHong Kong Inter-University Biochemistry Postgraduate Symposium Booklet 2013en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleSufu defines the balance of hindbrain progenitor cells maintenance and differentiationen_US
dc.typeConference_Paperen_US
dc.identifier.emailHor, HH: hhhor@hku.hken_US
dc.identifier.emailHui, CC: cchuilab@hku.hken_US
dc.identifier.emailSham, MH: mhsham@hku.hk-
dc.identifier.authoritySham, MH=rp00380en_US
dc.description.naturepostprint-
dc.identifier.hkuros216515en_US
dc.publisher.placeHong Kong-

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