Regulation of Axonal Elongation and Pathfinding from the Entorhinal Cortex to the Dentate Gyrus in the Hippocampus by the Chemokine Stromal Cell-Derived Factor 1α

Ohshima, Yoichi; Kubo, Takekazu; Koyama, Ryuta; Ueno, Masaki; Nakagawa, Masanori; Yamashita, Toshio

doi:10.1523/jneurosci.1670-08.2008

Cited by 26 publications

(21 citation statements)

References 41 publications

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“…53,54 Apart from its migratory function, SDF-1 has also been shown to be engaged in neuromodulation 17,55 and axonal elongation from the entorhinal cortex towards the dentate gyrus. 56 There is a species-specific predominance of particular splicing variants in the brain. In mice SDF-1β is the most abundant isoform, while in rats, it is SDF-1γ.…”

Section: Pathology-specific Rolementioning

confidence: 99%

Functional diversity of SDF-1 splicing variants

Janowski

2009

Cell Adhesion & Migration

113

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SDF-1 is ubiquitously expressed in vertebrate tissues in a constitutive manner. It performs an essential role in cell migration and proliferation as well as participates in tissue-specific physiological processes such as neuromodulation. It is also involved in many pathological processes including: HIV infection, metastatic malignancy, chronic inflammatory disorders and benign proliferative diseases. SDF-1 is mostly regulated at the splicing, and not transcriptional level. Different splicing variants share agonist potency to their cognate receptor, CXCR4, but are characterized by distinct properties. SDF-1α is the predominant isoform found in all organs, but undergoes rapid proteolysis in blood. SDF-1β is more resistant to blood-dependent degradation, stimulates angiogenesis and is present in highly vascularized organs such as: the liver, spleen and kidneys. In contrast, SDF-1γ is located in very active, less vascularized organs susceptible to infarction such as the heart and the brain. The understanding of the functional diversity of the different splicing variants will help in developing therapeutic strategies.

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Section: Pathology-specific Rolementioning

confidence: 99%

Functional diversity of SDF-1 splicing variants

Janowski

2009

Cell Adhesion & Migration

113

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“…Previous reports have shown that RGMa inhibits mammalian CNS neurite outgrowth in vitro (Brinks et al, 2004;Hata et al, 2006;Kubo et al, 2008;Ohshima et al, 2008;Yoshida et al, 2008). To evaluate the involvement of p120GAP in the long-term effects of RGMa, we performed two types of in vitro neurite outgrowth assays.…”

Section: The Involvement Of P120gap In Rgma-induced Neurite Outgrowthmentioning

confidence: 99%

“…It has been demonstrated that RGMa is expressed in the inner molecular layer of the hippocampal dentate gyrus and that it restricts the axonal extension of developmental entorhinal cortical neurons, thereby facilitating appropriate connection with the dentate gyrus (Brinks et al, 2004;Ohshima et al, 2008). Furthermore, a recent study reported that RGMa suppresses neurite outgrowth, branching, and synapse formation in cultured cortical neurons (Yoshida et al, 2008), suggesting that RGMa may contribute to the formation of a precise wiring pattern, such as the entorhino-hippocampal connection, by inhibiting both synapse formation in the inner molecular layer of the dentate gyrus and axonal extension of the entorhinal cortical neurons.…”

Section: Roles Of the Rgma-mediated Ras Inactivation In Neuronal Netwmentioning

confidence: 99%

“…The repulsive guidance molecule (RGM) is a developmental repulsive guidance protein that plays a role in axon pathfinding in chicken temporal retina (Monnier et al, 2002). RGMa, a mammalian homolog of chicken RGM, also shows neurite-repulsive ability, and a previous report has indicated that RGMa restricts the axonal extension of developmental entorhinal cortical neurons, thereby facilitating appropriate connection with the hippocampal dentate gyrus (Brinks et al, 2004;Ohshima et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Inactivation of Ras by p120GAP via Focal Adhesion Kinase Dephosphorylation Mediates RGMa-Induced Growth Cone Collapse

Endo¹,

Yamashita²

2009

J. Neurosci.

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The repulsive guidance molecule RGMa performs several functions in the developing and adult CNSs. RGMa, through its receptor neogenin, induces growth cone collapse and neurite outgrowth inhibition. Here, we demonstrate that RGMa binding to neogenin leads to the inactivation of Ras, which is required for the RGMa-mediated repulsive function in cortical neurons. This signal transduction is mediated by the Ras-specific GTPase-activating protein (GAP) p120GAP. The SH2 domain of p120GAP interacts with focal adhesion kinase (FAK), which is phosphorylated at Tyr-397. When the cells are stimulated with RGMa, FAK undergoes dephosphorylation at Tyr-397 and is dissociated from p120GAP, and this dissociation is followed by an increase in the interaction between p120GAP and GTP-Ras. In addition, the knockdown of p120GAP prevents RGMa-induced growth cone collapse and neurite outgrowth inhibition. Furthermore, RGMa stimulation induces Akt inactivation through p120GAP, and the expression of the constitutively active Akt prevents RGMa-induced growth cone collapse. Thus, RGMa binding to neogenin regulates p120GAP activity through FAK Tyr-397 dephosphorylation, leading to the inactivation of Ras and its downstream effector Akt, and this signal transduction plays a role in the RGMa-mediated repulsive function.

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“…However, Li et al [56] found that the final settlement of the DG granule precursor cells at the subgranular zone is not dependent on the SDF-1α/CXCR4 signaling. In addition, SDF-1α guides the growth of perforant fibers linking the entorhinal cortex with the DG in a neural circuit [58]. During the early postnatal period, SDF-1α is expressed in Cajal-Retzius cells on the upper and lower blades of the dentate and in the maturing dentate granule neurons, as well as in the meninges [59].…”

Section: Roles Of Sdf-1α/cxcr4 In Brain Developmentmentioning

confidence: 99%

Contribution of SDF-1a/CXCR4 Signaling to Brain Development and Glioma Progression

et al. 2013

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The SDF-1α/CXCR4 signaling maintains central nervous system homeostasis through the interaction with the neurotransmitter and neuropeptide systems, the neuroendocrine systems. Recently, the SDF-1α/CXCR4 signaling has been reported to present nonrandom distribution in brain development and glioma progression, which exerts differential regulations on the assembly, differentiation, and function of neural precursors, neurons, glial cells, as well as glioma cells. In the present review, we highlight current knowledge about multiple molecular signaling pathways associated with the SDF-1α/CXCR4 signaling in glioma. Not only is the expression of CXCR4 a key determinant of glioma progression, but SDF-1α is essential for site-specific invasive or metastatic processes. SDF-1α is the switch of the SDF-1α/CXCR4 signaling from the endocrine loop to the autocrine and/or local paracrine loop in glioma progression and brain development. Studies of SDF-1α/CXCR4 signaling in the field of brain development may provide valuable tactics for glioma treatment.

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Regulation of Axonal Elongation and Pathfinding from the Entorhinal Cortex to the Dentate Gyrus in the Hippocampus by the Chemokine Stromal Cell-Derived Factor 1α

Cited by 26 publications

References 41 publications

Functional diversity of SDF-1 splicing variants

Functional diversity of SDF-1 splicing variants

Inactivation of Ras by p120GAP via Focal Adhesion Kinase Dephosphorylation Mediates RGMa-Induced Growth Cone Collapse

Contribution of SDF-1a/CXCR4 Signaling to Brain Development and Glioma Progression

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