Thrombospondin 4 deficiency in mouse impairs neuronal migration in the early postnatal and adult brain

Girard, F; Eichenberger, Simone; Celio, Marco R.

doi:10.1016/j.mcn.2014.06.010

Cited by 34 publications

(33 citation statements)

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“…Several receptors and factors are expressed in V-SVZ and RMS astrocytes that could potentially alter microenvironment composition and signaling. These include extracellular matrix (ECM) proteins such as thrombospondin (Thbs1 and Thbs4) and tenascin-C (Tnc) (Jankovski and Sotelo, 1996;Girard et al, 2014) and signaling molecules such as Robo and Eph receptors along with Ephrin ligands (Kaneko et al, 2010;Ming and Song, 2011;Falcão et al, 2012;Gengatharan et al, 2016;Todd et al, 2017), which may be under transcriptional control of OTX2 (Gherzi et al, 1997;Boncinelli and Morgan, 2001;Hoch et al, 2015;Peña et al, 2017). Expression analysis on V-SVZ microdissection lysates from the scFv-Otx2 non-cell autonomous OTX2 knock-down model showed that EphrinA1, Thbs1, Thbs4 and Tnc were upregulated in V-SVZ ( Fig.…”

Section: Otx2 Regulates Astrocyte Factorsmentioning

confidence: 99%

OTX2 signals from the choroid plexus to regulate adult neurogenesis

Planques

Moreira

Dubreuil

et al. 2018

Preprint

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Proliferation and migration during adult neurogenesis are regulated by a microenvironment originating from local vasculature, from cerebrospinal fluid produced by the choroid plexus, and from local supporting cells including astrocytes. Here, we focus on the function of Otx2 homeoprotein transcription factor in the adult subventricular zone which generates olfactory bulb neurons. We find that Otx2 secreted by choroid plexus is transferred to supporting cells of the subventricular zone and rostral migratory stream. Deletion of Otx2 in choroid plexus reduces the number of olfactory bulb newborn neurons and modifies extracellular matrix components produced by astrocytes. By expressing secreted single-chain antibodies to sequester Otx2 in the cerebrospinal fluid, we obtain similar results, demonstrating the importance of non-cell autonomous Otx2 in adult neurogenesis and suggesting a pivotal role for astrocytes. By using in vitro astrocytes co-cultured with neurospheres, we show that Otx2 down-regulates tenascin-C expression and subsequently modifies neuroblast migration. Thus, we reveal a multi-level and non-cell autonomous role of a homeoprotein, and reinforce the idea of the choroid plexus as a key niche compartment affecting adult neurogenesis.not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/243659 doi: bioRxiv preprint first posted online Jan. 5, 2018; 2 Introduction Neurogenesis in the adult mouse brain provides continuous replacement of interneurons in olfactory bulbs (OB) and is important for olfaction-based learning 1 . Neural stem cells, located in the adult subventricular zone (aSVZ) lining the lateral cerebral ventricles, give rise to progenitor cells (neuroblasts) that migrate though the rostral migratory stream (RMS) to reach the OB where they differentiate as interneurons and integrate into the network. The RMS is composed of a compacted neuroblast network forming chains that migrate along blood vessels and are surrounded by astrocytic processes 2,3 . While it is clear that RMS-associated astrocytes interact with neuroblasts 4 , the role of astrocytes for neuroblast migration is not well known. Astrocytes are also located in the aSVZ and are thought to play a role as supporting cells for regulating the neurogenic niche microenvironment 5 . The niche is further influenced by extrinsic factors coming from local vasculature and the cerebrospinal fluid (CSF) 6 . Furthermore, neural stem cells interact directly with both vasculature and CSF 7 . Indeed, it has been shown that molecules within the CSF can control aSVZ neurogenesis by regulating cell proliferation 8 or migration 9 . Homeoproteins are key regulators of neurogenesis both during embryogenesis and adult neurogenesis 10,11 . This class of transcription factors have the property to act both cellautonomously and non-cell-autonomously after secretion and internalization in target cells. The Otx2 homeoprotein is exp...

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Section: Otx2 Regulates Astrocyte Factorsmentioning

confidence: 99%

OTX2 signals from the choroid plexus to regulate adult neurogenesis

Planques

Moreira

Dubreuil

et al. 2018

Preprint

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“…High levels of TSP4 have been detected in remodeling and failing hearts [3][4][5][6][7], several cancers [8][9][10][11][12][13], and atherosclerotic lesions [14]. Recently, new functions have been ascribed to TSP4 in cardiovascular system [5][6][7][14][15][16][17][18][19][20][21][22][23][24][25], cancer [8][9][10][11][12][24][25][26][27][28][29], and nervous system [30][31][32][33][34], but effects of TSP4 on cellular responses and the regulation of TSP4 expression remain poorly understood. For example, with an exception of TGF-beta [25], stimuli inducing TSP4 expression in tissues remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Effect of Thrombospondin-4 on Pro-inflammatory Phenotype Differentiation and Apoptosis in Macrophages

Rahman

Muppala

et al. 2019

Preprint

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Thrombospondin-4 (TSP4) attracted a lot of attention recently as a result of new functions identified for this matricellular protein in cardiovascular, muscular, and nervous systems. We have previously reported that TSP4 promotes local vascular inflammation in mouse atherosclerosis model. A common variant of TSP4, P387-TSP4, was associated with increased cardiovascular disease risk in human population studies. In a mouse atherosclerosis model, TSP4 had profound effect on accumulation of macrophages in lesions, which prompted us to examine its effects on macrophages, more in detail in this report.We examined the effects of A387-TSP-4 and P387-TSP-4 on mouse macrophages in cell culture and in vivo in the model of LPS-induced peritonitis. In tissues and in cell culture, TSP4 expression was associated with inflammation: TSP4 expression was upregulated in peritoneal tissues in LPS-induced peritonitis, and pro-inflammatory signals, INFg, GM-CSF, and LPS, induced TSP4 expression in macrophages in vivo and in cell culture. Deficiency in TSP-4 in macrophages from Thbs4 -/mice reduced the expression of pro-inflammatory macrophage markers, suggesting that TSP-4 facilitates macrophage differentiation into pro-inflammatory phenotype. Expression of TSP4, especially more active P387-TSP4, was associated with higher cellular apoptosis. Cultured macrophages displayed increased adhesion to TSP4 and reduced migration in presence of TSP4, and these responses were further increased with P387 variant.We concluded that TSP4 expression in tissue macrophages and in cultured macrophages increases their accumulation in tissues during the acute inflammatory process and supports macrophage differentiation into a pro-inflammatory phenotype. In a model of acute inflammation, TSP4 supports pro-inflammatory macrophage apoptosis, a response that is closely related to their pro-inflammatory activity and release of pro-inflammatory signals. P387-TSP4 was found to be more active form of TSP4 in all examined functions.

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“…TSP4 itself is required for cell adhesion and migration of diverse cell types, including neurons and vascular smooth muscle cells (37,38). Accordingly, TSP4 has been implicated in vascular inflammation and atherogenesis, acting at least in part by promoting macrophage recruitment into the neointima (39).…”

Section: Discussionmentioning

confidence: 99%

Serum stimulation of CCR7 chemotaxis due to coagulation factor XIIa-dependent production of high-molecular-weight kininogen domain 5

Ponda

Breslow

2016

Proc. Natl. Acad. Sci. U.S.A.

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Chemokines and their receptors play a critical role in immune function by directing cell-specific movement. C-C chemokine receptor 7 (CCR7) facilitates entry of T cells into lymph nodes. CCR7-dependent chemotaxis requires either of the cognate ligands C-C chemokine ligand 19 (CCL19) or CCL21. Although CCR7-dependent chemotaxis can be augmented through receptor up-regulation or by increased chemokine concentrations, we found that chemotaxis is also markedly enhanced by serum in vitro. Upon purification, the serum cofactor activity was ascribed to domain 5 of high-molecular-weight kininogen. This peptide was necessary and sufficient for accelerated chemotaxis. The cofactor activity in serum was dependent on coagulation factor XIIa, a serine protease known to induce cleavage of high-molecular-weight kininogen (HK) at sites of inflammation. Within domain 5, we synthesized a 24-amino acid peptide that could recapitulate the activity of intact serum through a mechanism distinct from up-regulating CCR7 expression or promoting chemokine binding to CCR7. This peptide interacts with the extracellular matrix protein thrombospondin 4 (TSP4), and antibodies to TSP4 neutralize its activity. In vivo, an HK domain 5 peptide stimulated homing of both T and B cells to lymph nodes. A circulating cofactor that is activated at inflammatory foci to enhance lymphocyte chemotaxis represents a powerful mechanism coupling inflammation to adaptive immunity.

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Thrombospondin 4 deficiency in mouse impairs neuronal migration in the early postnatal and adult brain

Cited by 34 publications

References 28 publications

OTX2 signals from the choroid plexus to regulate adult neurogenesis

OTX2 signals from the choroid plexus to regulate adult neurogenesis

Effect of Thrombospondin-4 on Pro-inflammatory Phenotype Differentiation and Apoptosis in Macrophages

Serum stimulation of CCR7 chemotaxis due to coagulation factor XIIa-dependent production of high-molecular-weight kininogen domain 5

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