Axonal commissures in the central nervous system: how to cross the midline?

Nawabi, Homaira; Castellani, Valérie

doi:10.1007/s00018-011-0691-9

Cited by 52 publications

(47 citation statements)

References 126 publications

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“…3h-i), suggesting that the endo-IWR-1 treatment might interfere with ventral midline formation. By analogy to the known roles of slit and netrin during axon guidance in the CNS of vertebrates and arthropods 32 , mild defects in ventral midline formation might explain the axon guidance defects that we observed in endo-IWR-1-treated embryos. Finally, we observed that Pdu-axin expression is strongly reduced in endo-IWR-1-treated embryos (Fig.…”

Section: Resultssupporting

confidence: 54%

Involvement of the Wnt/β-catenin pathway in neurectoderm architecture in Platynereis dumerilii

et al. 2013

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Signalling pathways are essential for the correct development of the central nervous system (CNS) in bilaterian animals. Here we show that in the CNS of the annelid Platynereis dumerilii, neural progenitor cells (NPCs) are located close to the ventral midline and express axin, a negative regulator of the Wnt/b-catenin pathway. Using pharmacological inhibitors, we observe that Wnt/b-catenin is required for the transition between proliferating NPCs and differentiating neurons. We also show that the Rho-associated kinase (Rok) is necessary for neurectoderm morphogenesis and ventral midline formation, and indirectly affects the distribution of the NPCs and the development of axonal scaffolds. Moreover, seven genes belonging to the planar cell polarity (PCP) pathway are expressed in the developing Platynereis neurectoderm, suggesting an involvement in its morphogenesis. When compared with previous studies in vertebrates, our data suggest that the involvement of the Wnt/b-catenin pathway in the control of neural cell proliferation/differentiation is ancestral to bilaterians.

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Section: Resultssupporting

confidence: 54%

Involvement of the Wnt/β-catenin pathway in neurectoderm architecture in Platynereis dumerilii

et al. 2013

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“…Expressed at the floor plate by glial cells, ephrin B3 acts with short-range activity, whereas Slit2/3 and Sema3B are secreted factors with potentially longer range activity. Combinations and sequences of ligand accessibility and guidance receptor availability are likely to play crucial roles in providing spatial and temporal coordination of guidance signals at the floor plate (Dickson and Zou, 2010;Kaplan et al, 2014;Nawabi and Castellani, 2011). In addition, the common use of Syk signaling would provide an efficient way to ensure the integration of the various guidance forces.…”

Section: Integration Of Guidance Signals By Itam-based Signalingmentioning

confidence: 99%

Syk kinases are required for spinal commissural axon repulsion at the midline via ephrin/Eph pathway

et al. 2016

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In the hematopoietic system, Syk family tyrosine kinases are essential components of immunoreceptor ITAM-based signaling. While there is increasing data indicating the involvement of immunoreceptors in neural functions, the contribution of Syk kinases remains obscure. Previously, we identified phosphorylated forms of Syk kinases in specialized populations of migrating neurons or projecting axons. Moreover, we identified ephrin/Eph as guidance molecules utilizing the ITAM-bearing CD3zeta (Cd247) and associated Syk kinases for the growth cone collapse response induced in vitro. Here, we show that in the developing spinal cord, Syk is phosphorylated in navigating commissural axons. By analyzing axon trajectories in open-book preparations of Sykmouse embryos, we show that Syk kinases are dispensable for attraction towards the midline but confer growth cone responsiveness to repulsive signals that expel commissural axons from the midline. Known to serve a repulsive function at the midline, ephrin B3/EphB2 are obvious candidates for driving the Syk-dependent repulsive response. Indeed, Syk kinases were found to be required for ephrin B3-induced growth cone collapse in cultured commissural neurons. In fragments of commissural neuron-enriched tissues, Syk is in a constitutively phosphorylated state and ephrin B3 decreased its level of phosphorylation. Direct pharmacological inhibition of Syk kinase activity was sufficient to induce growth cone collapse. In conclusion, Syk kinases act as a molecular switch of growth cone adhesive and repulsive responses.

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“…Although commissural neurons in the vertebrate and invertebrate central nervous system have provided us with a wealth of information on the molecular mechanism of axon guidance (Dickson and Gilestro, 2006;Evans and Bashaw, 2010;Nawabi and Castellani, 2011), knowledge of the intrinsic genetic programs employed is still limited. For instance, it has remained obscure whether the action of a single transcription factor can activate downstream molecular programs required for midline crossing, or whether the parallel actions of several transcription factors are needed for this task.…”

Section: Homeodomain Factor Selectively Expressed By Midbrain Commissmentioning

confidence: 99%

Dbx1 triggers crucial molecular programs required for midline crossing by midbrain commissural axons

Inamata

Shirasaki

2014

Development

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Axon guidance by commissural neurons has been well documented, providing us with a molecular logic of how midline crossing is achieved during development. Despite these advances, knowledge of the intrinsic genetic programs is still limited and it remains obscure whether the expression of a single transcription factor is sufficient to activate transcriptional programs that ultimately enable midline crossing. Here, we show in the mouse that the homeodomain transcription factor Dbx1 is expressed by a subset of progenitor cells that give rise to commissural neurons in the dorsal midbrain. Gainand loss-of-function analyses indicate that the expression of Dbx1 alone is sufficient and necessary to trigger midline crossing in vivo. We also show that Robo3 controls midline crossing as a crucial downstream effector of the Dbx1-activated molecular programs. Furthermore, Dbx1 suppresses the expression of the transcriptional program for ipsilateral neuron differentiation in parallel. These results suggest that a single transcription factor, Dbx1, has an essential function in assigning midline-crossing identity, thereby contributing crucially to the establishment of the wiring laterality in the developing nervous system.

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Axonal commissures in the central nervous system: how to cross the midline?

Cited by 52 publications

References 126 publications

Involvement of the Wnt/β-catenin pathway in neurectoderm architecture in Platynereis dumerilii

Involvement of the Wnt/β-catenin pathway in neurectoderm architecture in Platynereis dumerilii

Syk kinases are required for spinal commissural axon repulsion at the midline via ephrin/Eph pathway

Dbx1 triggers crucial molecular programs required for midline crossing by midbrain commissural axons

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