Sonic Hedgehog Guides Post-Crossing Commissural Axons Both Directly and Indirectly by Regulating Wnt Activity

Domanitskaya, Elena; Wacker, Andrin; Mauti, Olivier; Baeriswyl, Thomas; Esteve, Pilar; Bovolenta, Paola; Stoeckli, Esther T.

doi:10.1523/jneurosci.1488-10.2010

Cited by 71 publications

(82 citation statements)

References 32 publications

(59 reference statements)

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“…Previous research has shown involvement of Shh both in tissue patterning and in direct axon guidance, such as in spinal cord patterning and commissural axon guidance across and along the midline (Ericson et al, 1997;Briscoe and Ericson, 1999;Charron et al, 2003;Bourikas et al, 2005;Okada et al, 2006;Yam et al, 2009;Domanitskaya et al, 2010), as well as in optic stalk and retina patterning and RGC axon guidance along the retinotectal pathway (Ekker et al, 1995;Macdonald et al, 1995;Perron et al, 2003;Trousse et al, 2001;Kolpak et al, 2005;Kolpak et al, 2009;Sánchez-Camacho and Bovolenta, 2008;Fabre et al, 2010;Gordon et al, 2010). We determined that Hh signaling acts non-cell-autonomously for intraretinal axon pathfinding in zebrafish and that Hh pathway activity is required during early eye patterning for correct intraretinal pathfinding…”

Section: Discussionmentioning

confidence: 99%

Sonic hedgehog is indirectly required for intraretinal axon pathfinding by regulating chemokine expression in the optic stalk

Hörndli

Chien

2012

Development

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SUMMARYSuccessful axon pathfinding requires both correct patterning of tissues, which will later harbor axonal tracts, and precise localization of axon guidance cues along these tracts at the time of axon outgrowth. Retinal ganglion cell (RGC) axons grow towards the optic disc in the central retina, where they turn to exit the eye through the optic nerve. Normal patterning of the optic disc and stalk and the expression of guidance cues at this choice point are necessary for the exit of RGC axons out of the eye. Sonic hedgehog (Shh) has been implicated in both patterning of ocular tissue and direct guidance of RGC axons. Here, we examine the precise spatial and temporal requirement for Hedgehog (Hh) signaling for intraretinal axon pathfinding and show that Shh acts to pattern the optic stalk in zebrafish but does not guide RGC axons inside the eye directly. We further reveal an interaction between the Hh and chemokine pathways for axon guidance and show that cxcl12a functions downstream of Shh and depends on Shh for its expression at the optic disc. Together, our results support a model in which Shh acts in RGC axon pathfinding indirectly by regulating axon guidance cues at the optic disc through patterning of the optic stalk.

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Section: Discussionmentioning

confidence: 99%

Sonic hedgehog is indirectly required for intraretinal axon pathfinding by regulating chemokine expression in the optic stalk

Hörndli

Chien

2012

Development

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“…Axonal repulsion is induced by the upregulation of Robo1 on the growth cone surface, which allows for the detection of Slit, a negative floorplate-derived signal (Philipp et al, 2012). Axonal navigation at the floorplate exit site is subsequently directed by F-spondin (Burstyn-Cohen et al, 1999), SynCAMs/Nectin-like molecules (Niederkofler et al, 2010), MDGA2 (Joset et al, 2011), and the morphogens Wnts (Lyuksyutova et al, 2003;Domanitskaya et al, 2010) and sonic hedgehog (Shh) (Bourikas et al, 2005;Wilson and Stoeckli, 2013).…”

Section: Introductionmentioning

confidence: 99%

Semaphorin 6B acts as a receptor in post-crossing commissural axon guidance

et al. 2014

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Semaphorins are a large family of axon guidance molecules that are known primarily as ligands for plexins and neuropilins. Although class-6 semaphorins are transmembrane proteins, they have been implicated as ligands in different aspects of neural development, including neural crest cell migration, axon guidance and cerebellar development. However, the specific spatial and temporal expression of semaphorin 6B (Sema6B) in chick commissural neurons suggested a receptor role in axon guidance at the spinal cord midline. Indeed, in the absence of Sema6B, post-crossing commissural axons lacked an instructive signal directing them rostrally along the contralateral floorplate border, resulting in stalling at the exit site or even caudal turns. Truncated Sema6B lacking the intracellular domain was unable to rescue the loss-of-function phenotype, confirming a receptor function of Sema6B. In support of this, we demonstrate that Sema6B binds to floorplate-derived plexin A2 (PlxnA2) for navigation at the midline, whereas a cis-interaction between PlxnA2 and Sema6B on pre-crossing commissural axons may regulate the responsiveness of axons to floorplate-derived cues.

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“…For pre-crossing axons, Netrin1-DCC attraction (likely in conjunction with other midline attractants) predominates over repulsive signals to guide pre-crossing axons toward the midline. Commissural axons reach the midline, and while still being attracted to the floor plate Netrin1, their growth is promoted across the midline by cell adhesion molecules such as axonin-1 and NrCAM (Stoeckli et al, 1997). By the time they reach the far side, the growth cones have upregulated Robos and likely other repellent receptors.…”

Section: Discussionmentioning

confidence: 99%

“…An implication of this model is that post-crossing trajectories could be set at different positions by variations in the attraction-repulsion balance. In addition to dorsal-ventral positioning, the anterior-posterior direction of the post-crossing trajectories would involve responses to anteroposterior cue gradients, such as Shh and Wnt (Lyuksyutova et al, 2003;Domanitskaya et al, 2010;Yam et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Netrin1-DCC-Mediated Attraction Guides Post-Crossing Commissural Axons in the Hindbrain

2015

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Commissural axons grow along precise trajectories that are guided by several cues secreted from the ventral midline. After initial attraction to the floor plate using Netrin1 activation of its main attractive receptor, DCC (deleted in colorectal cancer), axons cross the ventral midline, and many turn to grow longitudinally on the contralateral side. After crossing the midline, axons are thought to lose their responsiveness to Netrin1 and become sensitive to midline Slit-Robo repulsion. We aimed to address the in vivo significance of Netrin1 in guiding post-crossing axon trajectories in mouse embryos. Surprisingly, in contrast to the spinal cord, Netrin1 and DCC mutants had abundant commissural axons crossing in the hindbrain. In Netrin1 and DCC mutants, many post-crossing axons made normal turns to grow longitudinally, but projected abnormally at angles away from the midline. In addition, exposure of cultured hindbrain explants to ectopic Netrin1 caused attractive deflection of post-crossing axons. Thus, Netrin1-DCC signaling is not required to attract pre-crossing axons toward the hindbrain floor plate, but is active in post-crossing guidance. Also in contrast with spinal cord, analysis of hindbrain post-crossing axons in Robo1/2 mutant embryos showed that Slit-Robo repulsive signaling was not required for post-crossing trajectories. Our findings show that Netrin1-DCC attractive signaling, but not Slit-Robo repulsive signaling, remains active in hindbrain postcrossing commissural axons to guide longitudinal trajectories, suggesting surprising regional diversity in commissural axon guidance mechanisms.

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Sonic Hedgehog Guides Post-Crossing Commissural Axons Both Directly and Indirectly by Regulating Wnt Activity

Cited by 71 publications

References 32 publications

Sonic hedgehog is indirectly required for intraretinal axon pathfinding by regulating chemokine expression in the optic stalk

Sonic hedgehog is indirectly required for intraretinal axon pathfinding by regulating chemokine expression in the optic stalk

Semaphorin 6B acts as a receptor in post-crossing commissural axon guidance

Netrin1-DCC-Mediated Attraction Guides Post-Crossing Commissural Axons in the Hindbrain

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