Repulsion and Attraction of Axons by Semaphorin3D Are Mediated by Different Neuropilins<i>In Vivo</i>

Wolman, Marc A.; Liu, Yan; Tawarayama, Hiroshi; Watanabe, Shôji; Halloran, Mary C.

doi:10.1523/jneurosci.2349-04.2004

Cited by 91 publications

(93 citation statements)

References 49 publications

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“…The MLF is initially formed by axons of the nucMLF, located in the ventral midbrain, that extend caudally through the hindbrain and into the spinal cord and serve as a scaffold on which multiple axon populations extend in the rostrocaudal axis. Previously, we showed that sema3D is expressed both rostral and medial to the nucMLF clusters before and during initial MLF axon extension (Halloran et al, 1999;Wolman et al, 2004) (Fig. 1 A).…”

Section: Sema3d Does Not Promote Mlf Fasciculation Via Repulsionmentioning

confidence: 70%

“…For example, semaphorins and slits are thought to drive fasciculation by creating a repulsive surround that channels axons into bundles and prevents their straying into nontarget tissues Taniguchi et al, 1997;Isbister et al, 1999;Giger et al, 2000;Ringstedt et al, 2000;Cloutier et al, 2002Cloutier et al, , 2004Hutson and Chien, 2002;Oster et al, 2003;Huber et al, 2005). However, we previously showed that knockdown of a repulsive semaphorin caused aberrant defasciculation of axons that are not normally bounded by its expression (Wolman et al, 2004), suggesting that semaphorins might also promote fasciculation via an unidentified mechanism.…”

Section: Introductionmentioning

confidence: 85%

“…Morpholino oligonucleotides (MOs) against sema3D, nrp1A, L1.1, L1.2, plexinA3, and plexinA4 were synthesized by Gene Tools (Corvallis, OR). Sequences for morpholinos targeting Sema3D (Sema3DMO or Sema3D splice MO), Nrp1A (Nrp1AMO), PlexinA3 (PlexinA3MO1), PlexinA4 (PlexinA4MO), and control morpholinos (CONMO, STDCON) have been reported previously and tested for efficacy Miyashita et al, 2004;Wolman et al, 2004;Liu and Halloran, 2005;Feldner et al, 2007). The sequences of morpholinos targeting L1.1 (L1.1MOA and L1.1MOB) and the L1.2 (L1.2MOA and L1.2MOB) morpholinos are as follows (with the sequence complementary to the start codon underlined or residue numbers in parentheses for sequences not overlapping with start codon):…”

Section: Methodsmentioning

confidence: 99%

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Semaphorin3D Regulates Axon–Axon Interactions by Modulating Levels of L1 Cell Adhesion Molecule

Wolman

Regnery²,

Becker³

et al. 2007

J. Neurosci.

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The decision of a growing axon to selectively fasciculate with and defasciculate from other axons is critical for axon pathfinding and target innervation. Fasciculation can be regulated by cell adhesion molecules that modulate interaxonal adhesion and repulsive molecules, expressed by surrounding tissues that channel axons together. Here we describe crosstalk between molecules that mediate these mechanisms. We show that Semaphorin3D (Sema3D), a classic repulsive molecule, promotes fasciculation by regulating L1 CAM levels and axon-axon interactions rather than by creating a repulsive surround. Knockdown experiments show that Sema3D and L1 genetically interact to promote fasciculation. Sema3D overexpression increases and Sema3D knockdown decreases levels of axonal L1 protein. Moreover, excess L1 rescues defasciculation caused by the loss of Sema3D. In vivo time-lapse imaging reveals that Sema3D or L1 knockdown cause identical defects in growth cone behaviors during axon-axon interactions, consistent with a loss of adhesion. These results reveal a novel mechanism by which a semaphorin promotes fasciculation and modulates axon-axon interactions by regulating an adhesion molecule.

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Section: Sema3d Does Not Promote Mlf Fasciculation Via Repulsionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

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Semaphorin3D Regulates Axon–Axon Interactions by Modulating Levels of L1 Cell Adhesion Molecule

Wolman

Regnery²,

Becker³

et al. 2007

J. Neurosci.

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“…Examination of the aberrant dorsal ADt axons suggests that Dcc is likely involved in the asymmetric outgrowth of the ADt neurons (Gao et al 2012). Previous studies have implicated other guidance factors such as neuropilins and semaphorin in the guidance of the anterior commissural axon to the midline (Wolman et al, 2004). These and other factors such as Neogenin, a guidance receptor related to Dcc (Wilson and Key, 2007;De Vries and Cooper, 2008), may partially compensate for the loss of the Dcc function to mediate the AC formation.…”

Section: Axonal Projection Patterns Of Adt Neurons Are Heterogeneousmentioning

confidence: 99%

“…Multiple guidance signals are involved in the formation of the AC and the SOT (Wolman et al, 2004;Wilson and Key, 2006). However, few studies have examined the heterogeneity of the telencephalic neurons, and it is unclear whether the individual axons choose specific projection paths at the intersection between the AC and the SOT.…”

Section: Introductionmentioning

confidence: 99%

Robo2–Slit and Dcc–Netrin1 Coordinate Neuron Axonal Pathfinding within the Embryonic Axon Tracts

et al. 2012

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In the embryonic vertebrate brain, early born neurons establish highly stereotyped embryonic axonal tracts along which the neuronal interconnections form. To understand the mechanism underlying neuron axonal pathfinding within the embryonic scaffold of axon tracts, we studied zebrafish anterior dorsal telencephalic (ADt) neuron development. While previous studies suggest the ADt neuronal axons extend along a commissural tract [anterior commissure (AC)] and a descending ipsilateral tract [supraoptic tract (SOT)], it is unclear whether individual ADt neuronal axons choose specific projection paths at the intersection between the AC and the SOT. We labeled individual ADt neurons using a forebrain-specific promoter to drive expression of fluorescent proteins. We found the ADt axonal projection patterns were heterogeneous and correlated with their soma positions. Our results suggest that cell intrinsic differences along the dorsal ventral axis of the telencephalon regulate the axonal projection choices. Next, we determined that the guidance receptors roundabout2 (Robo2) and deleted in colorectal cancer (Dcc) were differentially expressed in the ADt neurons. We showed that knocking down Robo2 function by injecting antisense morpholino oligonucleotides abolished the ipsilateral SOT originating from the ADt neurons. Knocking down Dcc function did not prevent formation of the AC and the SOT. In contrast, the AC was specifically reduced when Netrin1 function was knocked down. Further mechanistic studies suggested that Robo2 responded to the repellent Slit signals and suppressed the attractive Netrin signals. These findings demonstrate how Robo2-Slit and Dcc-Netrin coordinate the axonal projection choices of the developing neurons in the vertebrate forebrain.

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Cysteines in the neuropilin‐2 MAM domain modulate receptor homooligomerization and signal transduction

et al. 2015

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Neuropilins (NRPs) are transmembrane receptors involved in angiogenesis, lymphangiogenesis, and neuronal development as well as in cancer metastasis. Previous studies suggest that NRPs exist in heteromeric complexes with vascular endothelial growth factors (VEGFs) and VEGF receptors as well as plexins and semaphorins. We determined via site-directed mutagenesis and bioluminescent resonance energy transfer assays that a conserved cysteine (C711) in the Danio rerio NRP2a MAM (meprin, A-5 protein, and protein tyrosine phosphatase μ) domain modulates NRP2a homomeric interactions. Mutation of this residue also disrupts semaphorin-3F binding in NRP2a-transfected COS-7 cells and prevents the NRP2a overexpression effects in a zebrafish vascular model. Collectively, our results indicate the MAM domain plays an important role in defining the NRP2 homodimer structure, which is important for semaphorin-dependent signal transduction via NRP2.

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Repulsion and Attraction of Axons by Semaphorin3D Are Mediated by Different NeuropilinsIn Vivo

Cited by 91 publications

References 49 publications

Semaphorin3D Regulates Axon–Axon Interactions by Modulating Levels of L1 Cell Adhesion Molecule

Semaphorin3D Regulates Axon–Axon Interactions by Modulating Levels of L1 Cell Adhesion Molecule

Robo2–Slit and Dcc–Netrin1 Coordinate Neuron Axonal Pathfinding within the Embryonic Axon Tracts

Cysteines in the neuropilin‐2 MAM domain modulate receptor homooligomerization and signal transduction

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