Neuropilin 1-Sema Signaling Regulates Crossing of Cingulate Pioneering Axons during Development of the Corpus Callosum

Piper, Michael; Plachez, Céline; Zalucki, Oressia; Fothergill, Thomas; Goudreau, Guy; Erzurumlu, Reha S.; Gu, Chenghua; Richards, Linda J.

doi:10.1093/cercor/bhp027

Cited by 105 publications

(140 citation statements)

References 54 publications

(68 reference statements)

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“…Similar to E15.5-16.5 controls, callosal axons in Nf2 mutants were immunopositive for guidance receptors Neuropilin-1 (Piper et al, 2009b) and Dcc (Fazeli et al, 1997), and Robo1 (Andrews et al, 2006) transcripts were detected in the cell bodies of cingulate neurons (supplementary material Fig. S7A-F).…”

Section: Upregulation Of Slit2 Contributes To Callosal Agenesis In Nfmentioning

confidence: 63%

The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap

et al. 2014

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The corpus callosum connects cerebral hemispheres and is the largest axon tract in the mammalian brain. Callosal malformations are among the most common congenital brain anomalies and are associated with a wide range of neuropsychological deficits. Crossing of the midline by callosal axons relies on a proper midline environment that harbors guidepost cells emitting guidance cues to instruct callosal axon navigation. Little is known about what controls the formation of the midline environment. We find that two components of the Hippo pathway, the tumor suppressor Nf2 (Merlin) and the transcriptional coactivator Yap (Yap1), regulate guidepost development and expression of the guidance cue Slit2 in mouse. During normal brain development, Nf2 suppresses Yap activity in neural progenitor cells to promote guidepost cell differentiation and prevent ectopic Slit2 expression. Loss of Nf2 causes malformation of midline guideposts and Slit2 upregulation, resulting in callosal agenesis. Slit2 heterozygosity and Yap deletion both restore callosal formation in Nf2 mutants. Furthermore, selectively elevating Yap activity in midline neural progenitors is sufficient to disrupt guidepost formation, upregulate Slit2 and prevent midline crossing. The Hippo pathway is known for its role in controlling organ growth and tumorigenesis. Our study identifies a novel role of this pathway in axon guidance. Moreover, by linking axon pathfinding and neural progenitor behaviors, our results provide an example of the intricate coordination between growth and wiring during brain development.

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Section: Upregulation Of Slit2 Contributes To Callosal Agenesis In Nfmentioning

confidence: 63%

The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap

et al. 2014

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“…Alternatively, the dorsal shift of the PSPB might interfere with the projection of these neurons as they might be separated from attractive guidance cues emanating from the cortex (Ló pez-Bendito et al, 2006). Given the known role of pioneer neurons in the development of forebrain axonal connections (McConnell et al, 1989;De Carlos and O'Leary, 1992;Supèr et al, 1998;Lakhina et al, 2007;Piper et al, 2009), defective LGE pioneer development in Pdn/Pdn embryos provides a strong explanation for the delay of CTAs to cross the PSPB. In addition, the defective formation of the PSPB might provide an alternative, not mutually exclusive, explanation for the navigation defects of CTAs (Molnár and Blakemore, 1995a;Molnár and Butler, 2002).…”

Section: Discussionmentioning

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.

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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.

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“…Embryos were collected and fixed as described above (n ϭ 3 for both wild-type and knock-out). In situ hybridization was performed using antisense probes as previously described (Piper et al, 2009a) with minor modifications. The hybridization temperatures were 68 -70°C.…”

Section: Introductionmentioning

confidence: 99%

NFIA Controls Telencephalic Progenitor Cell Differentiation through Repression of the Notch Effector Hes1

Piper¹,

Barry²,

Hawkins³

et al. 2010

Journal of Neuroscience

135

145

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The balance between self-renewal and differentiation of neural progenitor cells is an absolute requirement for the correct formation of the nervous system. Much is known about both the pathways involved in progenitor cell self-renewal, such as Notch signaling, and the expression of genes that initiate progenitor differentiation. However, whether these fundamental processes are mechanistically linked, and specifically how repression of progenitor self-renewal pathways occurs, is poorly understood. Nuclear factor I A (Nfia), a gene known to regulate spinal cord and neocortical development, has recently been implicated as acting downstream of Notch to initiate the expression of astrocyte-specific genes within the cortex. Here we demonstrate that, in addition to activating the expression of astrocyte-specific genes, Nfia also downregulates the activity of the Notch signaling pathway via repression of the key Notch effector Hes1. These data provide a significant conceptual advance in our understanding of neural progenitor differentiation, revealing that a single transcription factor can control both the activation of differentiation genes and the repression of the self-renewal genes, thereby acting as a pivotal regulator of the balance between progenitor and differentiated cell states.

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Neuropilin 1-Sema Signaling Regulates Crossing of Cingulate Pioneering Axons during Development of the Corpus Callosum

Cited by 105 publications

References 54 publications

The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap

The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap

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

NFIA Controls Telencephalic Progenitor Cell Differentiation through Repression of the Notch Effector Hes1

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