Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern

Sonic hedgehog (Shh) signaling is essential for thalamic development. The Gli transcription factors act downstream of Shh – while Gli2 is the major activator (GliA), Gli3 acts primarily as a repressor (GliR). The thalamus is remarkable among dorsal structures because of its proximity to the mid-dien...

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Main Authors:	Haddad-Tóvolli, Roberta, Heide, Michael, Zhou, Xunlei, Blaess, Sandra, Alvarez-Bolado, Gonzalo
Format:	Online
Language:	English
Published:	Frontiers Research Foundation 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283895/

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spelling	pubmed-32838952012-02-27 Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern Haddad-Tóvolli, Roberta Heide, Michael Zhou, Xunlei Blaess, Sandra Alvarez-Bolado, Gonzalo Neuroscience Sonic hedgehog (Shh) signaling is essential for thalamic development. The Gli transcription factors act downstream of Shh – while Gli2 is the major activator (GliA), Gli3 acts primarily as a repressor (GliR). The thalamus is remarkable among dorsal structures because of its proximity to the mid-diencephalic organizer, a unique dorsal Shh source. This lends complexity to the interactions between Shh, Gli2, and Gli3, suggesting the presence of a dorsal Gli activator which elsewhere is found only ventrally, and making the dissection of thalamic Gli functions particularly interesting. A current model based on mutant phenotypes in telencephalon and midbrain postulates a degree of reciprocal antagonism of Shh and Gli3 in dorsal brain regions. To approach the role of Gli factors in thalamic specification we first analyzed mice deficient in Gli2 or Gli3. In Gli2 mutants, the thalamus is small and poorly differentiated with the exception of the medial and intralaminar nuclei which, in contrast, are specifically and severely affected by Gli3 inactivation. Gbx2 expression is very reduced in the Gli3 mutant. Most thalamic nuclei are present in both mutants, although incompletely differentiated, as reflected by the loss of specific markers. The ventral posterior group, revealed by novel specific marker Hes1, is present in both mutants and extends axons to the telencephalon. To test the Gli3/Shh interaction we generated a novel mutant deficient in Gli3 and neuroepithelial Shh. The thalamus of the n-Shh/Gli3 double mutants is very large and very poorly differentiated except for a broad domain of Gbx2, Lhx2, and Calb2 expression. In utero electroporation experiments on wild type embryos suggest that a stage-specific factor acting early is responsible for this prepattern. We show that, in the thalamus, GliA acts downstream of Shh to specify pattern and size of the thalamic nuclei to the exception of the medial and intralaminar groups. Gli3A can partially substitute for Gli2A in the Gli2 mutant. GliR is essential for specification and growth of the medial and intralaminar nuclei, contributes to the specification of other thalamic nuclei and reduces thalamic size. GliA (from neuroepithelial Shh signaling) and GliR do not show reciprocal antagonism in the thalamus, and their joint abolition does not rescue the wild type phenotype. Frontiers Research Foundation 2012-02-22 /pmc/articles/PMC3283895/ /pubmed/22371696 http://dx.doi.org/10.3389/fnins.2012.00027 Text en Copyright © 2012 Haddad-Tóvolli, Heide, Zhou, Blaess and Alvarez-Bolado. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Haddad-Tóvolli, Roberta Heide, Michael Zhou, Xunlei Blaess, Sandra Alvarez-Bolado, Gonzalo
spellingShingle	Haddad-Tóvolli, Roberta Heide, Michael Zhou, Xunlei Blaess, Sandra Alvarez-Bolado, Gonzalo Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern
author_facet	Haddad-Tóvolli, Roberta Heide, Michael Zhou, Xunlei Blaess, Sandra Alvarez-Bolado, Gonzalo
author_sort	Haddad-Tóvolli, Roberta
title	Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern
title_short	Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern
title_full	Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern
title_fullStr	Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern
title_full_unstemmed	Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern
title_sort	mouse thalamic differentiation: gli-dependent pattern and gli-independent prepattern
description	Sonic hedgehog (Shh) signaling is essential for thalamic development. The Gli transcription factors act downstream of Shh – while Gli2 is the major activator (GliA), Gli3 acts primarily as a repressor (GliR). The thalamus is remarkable among dorsal structures because of its proximity to the mid-diencephalic organizer, a unique dorsal Shh source. This lends complexity to the interactions between Shh, Gli2, and Gli3, suggesting the presence of a dorsal Gli activator which elsewhere is found only ventrally, and making the dissection of thalamic Gli functions particularly interesting. A current model based on mutant phenotypes in telencephalon and midbrain postulates a degree of reciprocal antagonism of Shh and Gli3 in dorsal brain regions. To approach the role of Gli factors in thalamic specification we first analyzed mice deficient in Gli2 or Gli3. In Gli2 mutants, the thalamus is small and poorly differentiated with the exception of the medial and intralaminar nuclei which, in contrast, are specifically and severely affected by Gli3 inactivation. Gbx2 expression is very reduced in the Gli3 mutant. Most thalamic nuclei are present in both mutants, although incompletely differentiated, as reflected by the loss of specific markers. The ventral posterior group, revealed by novel specific marker Hes1, is present in both mutants and extends axons to the telencephalon. To test the Gli3/Shh interaction we generated a novel mutant deficient in Gli3 and neuroepithelial Shh. The thalamus of the n-Shh/Gli3 double mutants is very large and very poorly differentiated except for a broad domain of Gbx2, Lhx2, and Calb2 expression. In utero electroporation experiments on wild type embryos suggest that a stage-specific factor acting early is responsible for this prepattern. We show that, in the thalamus, GliA acts downstream of Shh to specify pattern and size of the thalamic nuclei to the exception of the medial and intralaminar groups. Gli3A can partially substitute for Gli2A in the Gli2 mutant. GliR is essential for specification and growth of the medial and intralaminar nuclei, contributes to the specification of other thalamic nuclei and reduces thalamic size. GliA (from neuroepithelial Shh signaling) and GliR do not show reciprocal antagonism in the thalamus, and their joint abolition does not rescue the wild type phenotype.
publisher	Frontiers Research Foundation
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283895/
_version_	1611507506407800832

Mouse Thalamic Differentiation: Gli-Dependent Pattern and Gli-Independent Prepattern

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