Draxin, a Repulsive Guidance Protein for Spinal Cord and Forebrain Commissures

Islam, Shahidul; Shinmyo, Yohei; Okafuji, Tatsuya; Su, Yuhong; Naser, Iftekhar Bin; Ahmed, Giasuddin; Zhang, Sanbing; Chen, Sandy; Ohta, Kunimasa; Kanazawa, Hiroshi; Abe, Takaya; Tanaka, Satomi; Nishinakamura, Ryuichi; Terashima, Toshio; Kitamura, Toshio; Tanaka, Hideaki

doi:10.1126/science.1165187

Cited by 153 publications

(217 citation statements)

References 15 publications

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“…Recent studies have shown that draxin is a repulsive guidance cue involved in commissural axon projection in the developing nervous system (60). Interestingly, draxin binds multiple netrin receptors: DCC, neurogenin, UNC5, and DSCAM, and the interaction of draxin and DCC is required for draxin-mediated neurite outgrowth and guidance (61).…”

Section: Discussionmentioning

confidence: 99%

Down Syndrome Cell Adhesion Molecule (DSCAM) Associates with Uncoordinated-5C (UNC5C) in Netrin-1-mediated Growth Cone Collapse

Purohit

et al. 2012

Journal of Biological Chemistry

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Background: Coordination of the signaling cascades downstream of netrin receptors is essential in axon guidance. Results: DSCAM collaborates with UNC5C to mediate netrin-1-induced axon growth cone collapse through the assembly of a signaling complex involving Fyn, FAK, and PAK1. Conclusion: DSCAM functions as a repulsive netrin receptor. Significance: Understanding the coordination of axon guidance signaling provides insight into the formation of precise neuronal circuitry during brain development.

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Section: Discussionmentioning

confidence: 99%

Down Syndrome Cell Adhesion Molecule (DSCAM) Associates with Uncoordinated-5C (UNC5C) in Netrin-1-mediated Growth Cone Collapse

Purohit

et al. 2012

Journal of Biological Chemistry

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“…In addition, we recently demonstrated that cingulate callosal axons also express the axon guidance receptor DCC, and that these axons are attracted towards its ligand, NTN1, at the midline (Fothergill et al, 2014). Similarly, other short-and longrange axon guidance molecules have been demonstrated to function in regulating neocortical callosal pathfinding (Shu and Richards, 2001;Shu et al, 2003;Andrews et al, 2006;Islam et al, 2009;Nishikimi et al, 2011). As callosal axons from the dorso-lateral cortex, where Nrp1 expression is absent, are able to project their axons medially (Zhou et al, 2013), it appears likely that other axon guidance mechanisms can guide callosal pathfinding in the absence of Nrp1 expression.…”

Section: Emx1 Mediates Cingulate Callosal Axon Guidance By Regulatingmentioning

confidence: 99%

EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex

et al. 2015

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Transcription factors act during cortical development as master regulatory genes that specify cortical arealization and cellular identities. Although numerous transcription factors have been identified as being crucial for cortical development, little is known about their downstream targets and how they mediate the emergence of specific neuronal connections via selective axon guidance. The EMX transcription factors are essential for early patterning of the cerebral cortex, but whether EMX1 mediates interhemispheric connectivity by controlling corpus callosum formation remains unclear. Here, we demonstrate that in mice on the C57Bl/6 background EMX1 plays an essential role in the midline crossing of an axonal subpopulation of the corpus callosum derived from the anterior cingulate cortex. In the absence of EMX1, cingulate axons display reduced expression of the axon guidance receptor NRP1 and form aberrant axonal bundles within the rostral corpus callosum. EMX1 also functions as a transcriptional activator of Nrp1 expression in vitro, and overexpression of this protein in Emx1 knockout mice rescues the midline-crossing phenotype. These findings reveal a novel role for the EMX1 transcription factor in establishing cortical connectivity by regulating the interhemispheric wiring of a subpopulation of neurons within the mouse anterior cingulate cortex.

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“…S7A-F). Midline guidance cues Sema3c (Niquille et al, 2009;Piper et al, 2009b), Netrin1 (Serafini et al, 1996) and Draxin (Islam et al, 2009) were expressed normally in Nf2 mutants (supplementary material Fig. S7G-L).…”

Section: Upregulation Of Slit2 Contributes To Callosal Agenesis In Nfmentioning

confidence: 99%

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

Lavado¹,

Ware²,

Paré³

et al. 2014

Journal of Cell Science

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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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Draxin, a Repulsive Guidance Protein for Spinal Cord and Forebrain Commissures

Cited by 153 publications

References 15 publications

Down Syndrome Cell Adhesion Molecule (DSCAM) Associates with Uncoordinated-5C (UNC5C) in Netrin-1-mediated Growth Cone Collapse

Down Syndrome Cell Adhesion Molecule (DSCAM) Associates with Uncoordinated-5C (UNC5C) in Netrin-1-mediated Growth Cone Collapse

EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex

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

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