Bone morphogenetic proteins mediate cellular response and, together with Noggin, regulate astrocyte differentiation after spinal cord injury

Xiao, Qi; Du, Yang; Wu, Wutian; Yip, Henry K.

doi:10.1016/j.expneurol.2009.12.003

Cited by 77 publications

(77 citation statements)

References 37 publications

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“…To further analyze the effect of KHS101 on lineage-specific differentiation, we exposed rat NPCs to the astrocyte-inducing cytokine bone morphogenetic protein 4 (BMP4), which is expressed in the adult neurogenic niches and has been reported to inhibit hippocampal neurogenesis (13)(14)(15)(16). As expected, BMP4 (50 ng/mL) treatment for 4 d increased differentiation to astrocytes (from 0.5 to 10%) within NPC cultures as assessed by immunostaining for the astrocyte marker glial fibrillary acidic protein (GFAP).…”

Section: Khs101 Suppresses Astrocyte Formation In Cultured Npcsmentioning

confidence: 99%

A small molecule accelerates neuronal differentiation in the adult rat

Wurdak

Zhu

Min

et al. 2010

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

106

108

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Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain. However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brain and resulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention directed at endogenous NPCs.

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Section: Khs101 Suppresses Astrocyte Formation In Cultured Npcsmentioning

confidence: 99%

A small molecule accelerates neuronal differentiation in the adult rat

Wurdak

Zhu

Min

et al. 2010

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

106

108

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“…The noggin could increase differentiation of NPCs into neurons/oligodendrocytes at the expense of astrocytes in vitro. The maturation of oligodendrocytes promoted by noggin should be conducive to the development of the nervous system (Xiao et al 2010). To identify whether BMPs are the mediators for the serum-induced astrocyte differentiation of OPCs, we used noggin to block the effect of serum on astroglial differentiation of OPCs.…”

Section: Discussionmentioning

confidence: 99%

BMP Signaling Mediates Astrocyte Differentiation of Oligodendrocyte Progenitor Cells

Lü

Wang

et al. 2010

Tohoku J. Exp. Med.

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Oligodendrocyte precursor cells (OPCs) can differentiate into oligodendrocytes or astrocytes, depending on cellular microenvironments. OPCs, cultured in medium supplemented with 10% (v/v) fetal bovine serum (FBS), give rise to type II astrocytes that express glial fibrillary acidic protein and a cell surface ganglioside that is recognized by A2B5 monoclonal antibody. However, the factors in FBS that direct the astrocyte differentiation are not determined. Moreover, bone morphogenetic proteins (BMPs) have been reported to be involved in astrocyte differentiation of neural progenitor cells. We therefore examined whether BMPs are responsible for the serum-mediated astrocyte differentiation from OPCs. OPCs were isolated from the spinal cords of Wistar rat embryos (at day 14) using the A2B5 antibody. We measured the concentrations of BMP-2 and BMP-4 in FBS and rat and human sera and the expression of mRNAs for three types of BMP receptors (BMPRIa, Ib and II) in OPCs by RT-PCR. The serum samples of the three species contained BMP-2 and BMP-4, as judged by ELISA with each monoclonal antibody, and the BMP receptor mRNAs are expressed in OPCs. When OPCs were cultured in the medium containing 10% FBS, cells (more than 95%) differentiated into type II astrocytes. However, when OPCs were pretreated with noggin, a soluble antagonist of BMP action, the degree of astrocyte differentiation was markedly decreased from 95.39 to 38.36%. Taken together, these results suggest that BMP signaling may be responsible for the serummediated astrocyte differentiation of OPCs. Our findings provide new insights into the molecular basis of differentiation of OPCs.

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“…Alternatively, damaged neurons may release signals recruiting astroglia and Olig21 glia in the mouse telencephalon but not in zebrafish, such as e.g. IL-6 or BMP-potent factors eliciting reactive astrogliosis (Fuller et al, 2007;Xiao et al, 2010). Thus, after having characterized the key cellular reactions taking place upon stab wound injury in the present work, it will now be important to elucidate the differences in the molecular signature of the cells reacting to injury in the zebrafish brain, involving mostly the microglia, and how their expression profile may differ from the activated microglia in the mammalian system.…”

Section: Gliosis and Repairmentioning

confidence: 99%

Stab wound injury of the zebrafish telencephalon: A model for comparative analysis of reactive gliosis

Baumgart

Barbosa

Bally‐Cuif

et al. 2011

Glia

169

228

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Reactive glia, including astroglia and oligodendrocyte progenitors (OPCs) are at the core of the reaction to injury in the mammalian brain with initially beneficial and later partially adverse functions such as scar formation. Given the different glial composition in the adult zebrafish brain with radial ependymoglia but no parenchymal astrocytes, we examined the glial response to an invasive stab wound injury model in the adult zebrafish telencephalon. Strikingly, already a few days after injury the wound was closed without any scar tissue. Similar to mammals, microglia cells reacted first and accumulated close to the injury site, while neither GFAP+ radial ependymoglia nor adult OPCs were recruited to the injury site. Moreover, OPCs failed to increase their proliferation after this injury, while the number of proliferating GFAP+ glia was increased until 7 days after injury. Importantly, neurogenesis was also increased after injury, generating additional neurons recruited to the parenchyma which survived for several months. Thus, these data suggest that the specific glial environment in the adult zebrafish telencephalon is not only permissive for long-term neuronal survival, but avoids scar formation. Invasive injury in the adult zebrafish telencephalon may therefore provide a useful model to untangle the molecular mechanisms involved in these beneficial glial reactions.

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Bone morphogenetic proteins mediate cellular response and, together with Noggin, regulate astrocyte differentiation after spinal cord injury

Cited by 77 publications

References 37 publications

A small molecule accelerates neuronal differentiation in the adult rat

A small molecule accelerates neuronal differentiation in the adult rat

BMP Signaling Mediates Astrocyte Differentiation of Oligodendrocyte Progenitor Cells

Stab wound injury of the zebrafish telencephalon: A model for comparative analysis of reactive gliosis

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