Lamination of the cerebral cortex is disturbed in Gli3 mutant mice

Friedrichs, Melanie; Larralde, Osmany; Skutella, Thomas; Theil, Thomas

doi:10.1016/j.ydbio.2008.03.032

Cited by 21 publications

(21 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The generation of CR cells is impaired in Gli3 mutant embryos, with the loss of caudal signals resulting in a substantial decrease in p73a + CR cells and in a derepression of Dbx1 in the dorsolateral pallium, which adopts a VP-like identity (Friedrichs et al, 2008;Hanashima et al, 2007;Theil, 2005). In agreement with these previous studies, we observed ectopic clusters of Er81 + CR cells in the lateral cortex in the Gli3 mutant (data not shown).…”

Section: Er81supporting

confidence: 92%

“…These signalling centres secrete morphogens that provide positional and proliferative cues to the surrounding telencephalic neuroepithelium (O'Leary et al, 2007;Rash and Grove, 2006;Sur and Rubenstein, 2005). Recently, the signals produced by the CH in the caudomedial telencephalon, which include TGFb molecules, were shown to be necessary for the generation of caudal CR cells (Friedrichs et al, 2008;Hanashima et al, 2007;Siegenthaler and Miller, 2008;Theil, 2005). Morphogens produced by the commissural plate (CoP) in the RM telencephalon and by the putative anti-hem in the lateral telencephalon might similarly participate in CR cell generation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells

et al. 2010

View full text Add to dashboard Cite

SUMMARYCajal-Retzius (CR) cells play a key role in the formation of the cerebral cortex. These pioneer neurons are distributed throughout the cortical marginal zone in distinct graded distributions. Fate mapping and cell lineage tracing studies have recently shown that CR cells arise from restricted domains of the pallial ventricular zone, which are associated with signalling centres involved in the early regionalisation of the telencephalic vesicles. In this study, we identified a subpopulation of CR cells in the rostral telencephalon that expresses Er81, a downstream target of Fgf8 signalling. We investigated the role of the rostral telencephalic patterning centre, which secretes FGF molecules, in the specification of these cells. Using pharmacological inhibitors and genetic inactivation of Fgf8, we showed that production of Fgf8 by the rostral telencephalic signalling centre is required for the specification of the Er81 + CR cell population. Moreover, the analysis of Fgf8 gain-of-function in cultivated mouse embryos and of Emx2 and Gli3 mutant embryos revealed that ectopic Fgf8 signalling promotes the generation of CR cells with a rostral phenotype from the dorsal pallium. These data showed that Fgf8 signalling is both required and sufficient to induce rostral CR cells. Together, our results shed light on the mechanisms specifying rostral CR cells and further emphasise the crucial role of telencephalic signalling centres in the generation of distinct CR cell populations.

show abstract

Section: Er81supporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells

et al. 2010

View full text Add to dashboard Cite

show abstract

“…3G), is shifted dorsally in the Pdn/Pdn telencephalon and expands into more dorsal regions of the neocortex (Fig. 3G,H) as in other Gli3 mutants (Hanashima et al, 2007;Friedrichs et al, 2008). These marker analyses indicate that the boundary between ventral and dorsal telencephalon is defective, with the PSPB becoming less defined and shifted dorsally in Pdn/Pdn mutants.…”

Section: Resultsmentioning

confidence: 69%

“…Similarly, Gli transcription factors, critical components of the Shh signaling pathway, are required for telencephalic development. Mutations in Gli3, in particular, affect the development of both ventral and dorsal components of the telencephalon (Grove et al, 1998;Theil et al, 1999;Tole et al, 2000;Kuschel et al, 2003;Theil, 2005;Fotaki et al, 2006;Friedrichs et al, 2008;Quinn et al, 2009;Yu et al, 2009a). In the dorsal telencephalon, Gli3 controls patterning independently of Shh, but in the VT, Gli3 transcription and cleavage of Gli3 protein into its repressor form are suppressed by Shh signaling, resulting in a dorsal high to ventral low gradient of Gli3 expression.…”

Section: Introductionmentioning

confidence: 99%

TheGli3Hypomorphic MutationPdnCauses Selective Impairment in the Growth, Patterning, and Axon Guidance Capability of the Lateral Ganglionic Eminence

Magnani¹,

Hasenpusch‐Theil²,

Jacobs³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

Previous studies have defined a requirement for Sonic hedgehog (Shh) signaling in patterning the ventral telencephalon, a major source of the neuronal diversity found in the mature telencephalon. The zinc finger transcription factor Gli3 is a critical component of the Shh signaling pathway and its loss causes major defects in telencephalic development. Gli3 is expressed in a graded manner along the dorsoventral axis of the telencephalon but it is unknown whether Gli3 expression levels are important for dorsoventral telencephalic patterning. To address this, we used the Gli3 hypomorphic mouse mutant Polydactyly Nagoya (Pdn). We show that in Pdn/Pdn embryos, the telencephalic expression of Gli3 remains graded, but Gli3 mRNA and protein levels are reduced, resulting in an upregulation of Shh expression and signaling. These changes mainly affect the development of the lateral ganglionic eminence (LGE), with some disorganization of the medial ganglionic eminence mantle zone. The pallial/subpallial boundary is shifted dorsally and the production of postmitotic neurons is reduced. Moreover, LGE pioneer neurons that guide corticofugal axons into the LGE do not form properly, delaying the entry of corticofugal axons into the ventral telencephalon. Pdn/Pdn mutants also show severe pathfinding defects of thalamocortical axons in the ventral telencephalon. Transplantation experiments demonstrate that the intrinsic ability of the Pdn ventral telencephalon to guide thalamocortical axons is compromised. We conclude that correct Gli3 levels are particularly important for the LGE's growth, patterning, and development of axon guidance capabilities.

show abstract

“…However, there are also important phenotypic differences. In contrast to Xt J mutants, invagination and specification of dorsomedial structures (e.g., choroid plexus, cortical hem) occurs to some extent in the cbs mutant, similar to Gli3 hypomorphic mutants (Kuschel et al, 2003;Friedrichs et al, 2008). Also, Emx1 and Emx2 expression are retained in the neocortex of the cbs mutant (Fig.…”

Section: Discussionmentioning

confidence: 85%

A Crucial Role for Primary Cilia in Cortical Morphogenesis

Willaredt¹,

Hasenpusch‐Theil²,

Gardner³

et al. 2008

J. Neurosci.

121

152

View full text Add to dashboard Cite

Primary cilia are important sites of signal transduction involved in a wide range of developmental and postnatal functions. Proteolytic processing of the transcription factor Gli3, for example, occurs in primary cilia, and defects in intraflagellar transport (IFT), which is crucial for the maintenance of primary cilia, can lead to severe developmental defects and diseases. Here we report an essential role of primary cilia in forebrain development. Uncovered by N-ethyl-N-nitrosourea-mutagenesis, cobblestone is a hypomorphic allele of the IFT gene Ift88, in which Ift88 mRNA and protein levels are reduced by 70 -80%. cobblestone mutants are distinguished by subpial heterotopias in the forebrain. Mutants show both severe defects in the formation of dorsomedial telencephalic structures, such as the choroid plexus, cortical hem and hippocampus, and also a relaxation of both dorsal-ventral and rostral-caudal compartmental boundaries. These defects phenocopy many of the abnormalities seen in the Gli3 mutant forebrain, and we show that Gli3 proteolytic processing is reduced, leading to an accumulation of the full-length activator isoform. In addition, we observe an upregulation of canonical Wnt signaling in the neocortex and in the caudal forebrain. Interestingly, the ultrastructure and morphology of ventricular cilia in the cobblestone mutants remains intact. Together, these results indicate a critical role for ciliary function in the developing forebrain.

show abstract

Lamination of the cerebral cortex is disturbed in Gli3 mutant mice

Cited by 21 publications

References 72 publications

Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells

Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells

TheGli3Hypomorphic MutationPdnCauses Selective Impairment in the Growth, Patterning, and Axon Guidance Capability of the Lateral Ganglionic Eminence

A Crucial Role for Primary Cilia in Cortical Morphogenesis

Contact Info

Product

Resources

About