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Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia

1,2,†, 1,† and 1,*
1
Department of Biology, Eberly College of Sciences, Center for Cellular Dynamics, Huck Institute of Life Science, The Penn State University, University Park, PA 16802, USA
2
Department of Occupational Health, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Dev. Biol. 2019, 7(1), 5; https://doi.org/10.3390/jdb7010005
Received: 2 November 2018 / Revised: 13 February 2019 / Accepted: 16 February 2019 / Published: 19 February 2019
(This article belongs to the Collection Hedgehog Signaling in Embryogenesis)
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Abstract

The primary cilia play essential roles in Hh-dependent Gli2 activation and Gli3 proteolytic processing in mammals. However, the roles of the cilia in Gli1 activation remain unresolved due to the loss of Gli1 transcription in cilia mutant embryos, and the inability to address this question by overexpression in cultured cells. Here, we address the roles of the cilia in Gli1 activation by expressing Gli1 from the Gli2 locus in mouse embryos. We find that the maximal activation of Gli1 depends on the cilia, but partial activation of Gli1 by Smo-mediated Hh signaling exists in the absence of the cilia. Combined with reduced Gli3 repressors, this partial activation of Gli1 leads to dorsal expansion of V3 interneuron and motor neuron domains in the absence of the cilia. Moreover, expressing Gli1 from the Gli2 locus in the presence of reduced Sufu has no recognizable impact on neural tube patterning, suggesting an imbalance between the dosages of Gli and Sufu does not explain the extra Gli1 activity. Finally, a non-ciliary Gli2 variant present at a higher level than Gli1 when expressed from the Gli2 locus fails to activate Hh pathway ectopically in the absence of the cilia, suggesting that increased protein level is unlikely the major factor underlying the ectopic activation of Hh signaling by Gli1 in the absence of the cilia. View Full-Text
Keywords: Hh signaling; Shh; neural tube; patterning; intraflagellar transport; Gli3; Sufu; Smo; mouse Hh signaling; Shh; neural tube; patterning; intraflagellar transport; Gli3; Sufu; Smo; mouse
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Wang, Y.; Zeng, H.; Liu, A. Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia. J. Dev. Biol. 2019, 7, 5.

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