MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex

Tseng, Kuan-Yin; Danilova, Tatiana; Domanskyi, Andrii; Saarma, Märt; Lindahl, Maria; Airavaara, Mikko

doi:10.1523/eneuro.0214-17.2017

Cited by 50 publications

(48 citation statements)

References 62 publications

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“…Previously, we reported impairments in the cortical development of Manf -/brain, but the adult cortex is morphologically normal (Tseng et al, 2017). Our results here show increased UPR activation in the brain of Manf -/mice during embryonic and postnatal development, but activation seems to gradually decrease after birth.…”

supporting

confidence: 64%

“…Later, it was reported that in the Nestin Cre/1 line used, recombination is observed in neural stem cells and neural progenitor cells from E12.5 but with incomplete efficiency (Dubois et al, 2006). Since MANF is mainly expressed in neurons in the adult mouse brain (Lindholm et al, 2008;Tseng et al, 2017;Danilova et al, 2019a,b), this recombination is expected to remove most of the MANF in the brain. Consequently, qPCR analysis showed barely detectable levels of Manf mRNA analyzed from the brain lysates from different brain areas of Manf fl/fl ::Nestin Cre/1 mice compared with littermate Manf fl/fl mice ( Fig.…”

Section: Conditional Deletion Of Manf In the Nervous Systemmentioning

confidence: 99%

“…We have shown that conventional MANF knock-out (KO) mice and pancreas-specific conditional KO mice develop insulin-dependent diabetes due to prolonged ER stress in pancreatic b cells, leading to loss of the b cell mass and premature death (Lindahl et al, 2014;Danilova et al, 2019a). In MANF KO mice, it was also demonstrated that MANF regulates cortical development and migration of neuronal progenitor cells (Tseng et al, 2017). Despite the suggested role of increased UPR activation behind impaired cortical development, the role of MANF in the regulation of UPR in neurons in vivo has remained unsolved.…”

Section: Introductionmentioning

confidence: 99%

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MANF Ablation Causes Prolonged Activation of the UPR without Neurodegeneration in the Mouse Midbrain Dopamine System

Pakarinen

Danilova

Võikar

et al. 2020

eNeuro

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Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) localized protein that regulates ER homeostasis and unfolded protein response (UPR). The biology of endogenous MANF in the mammalian brain is unknown and therefore we studied the brain phenotype of MANF-deficient female and male mice at different ages focusing on the midbrain dopamine system and cortical neurons. We show that a

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supporting

confidence: 64%

Section: Conditional Deletion Of Manf In the Nervous Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MANF Ablation Causes Prolonged Activation of the UPR without Neurodegeneration in the Mouse Midbrain Dopamine System

Pakarinen

Danilova

Võikar

et al. 2020

eNeuro

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“…) and human neural stem cells (hNSC) (Tseng et al . ). Furthermore, chemical induction of ER stress (by brefeldin A, thapsigargin, or tunicamyin) facilitates neurogenesis and neuronal differentiation at the expense of gliogenesis and glial differentiation, respectively, in P19 cells (Kawada et al .…”

Section: Factors Influencing Symmetric Versus Asymmetric Divisionmentioning

confidence: 97%

“…), and hNSC (Tseng et al . ). These findings are corroborated by accumulating in vivo reports of spatio‐temporal expression of distinct UPR effectors that are associated with the regulation of UPR signaling, which correlates with milestones of murine corticogenesis that suggests physiological functions of UPR in neuronal commitment and cell fate acquisition (Atf4 (Frank et al .…”

Section: Factors Influencing Symmetric Versus Asymmetric Divisionmentioning

confidence: 97%

Cortical progenitor biology: key features mediating proliferation versus differentiation

Uzquiano

Gladwyn-Ng

Nguyen

et al. 2018

Journal of Neurochemistry

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The cerebral cortex is a highly organized structure whose development depends on diverse progenitor cell types, namely apical radial glia, intermediate progenitors, and basal radial glia cells, which are responsible for the production of the correct neuronal output. In recent years, these progenitor cell types have been deeply studied, particularly basal radial glia and their role in cortical expansion and gyrification. We review here a broad series of factors that regulate progenitor behavior and daughter cell fate. We first describe the different neuronal progenitor types, emphasizing the differences between lissencephalic and gyrencephalic species. We then review key factors shown to influence progenitor proliferation versus differentiation, discussing their roles in progenitor dynamics, neuronal production, and potentially brain size and complexity. Although spindle orientation has been considered a critical factor for mode of division and daughter cell output, we discuss other features that are emerging as crucial for these processes such as organelle and cell cycle dynamics. Additionally, we highlight the importance of adhesion molecules and the polarity complex for correct cortical development. Finally, we briefly discuss studies assessing progenitor multipotency and its possible contribution to the production of specific neuronal populations. This review hence summarizes recent aspects of cortical progenitor cell biology, and pinpoints emerging features critical for their behavior.

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Upregulating HIF‐1α to Boost the Survival of Neural Stem Cells via Functional Peptides‐Complexed MRI‐Visible Nanomedicine for Stroke Therapy

Wang

Cai

Zhang

et al. 2022

Adv Healthcare Materials

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Neural stem cells (NSCs) transplantation has been considered as a promising strategy for the treatment of ischemic stroke. However, the therapeutic prospect is limited by the poor control over the survival, migration, and maturation of transplanted NSCs. Upregulating hypoxia inducible factor (HIF)-1𝜶 expression in stem cells can improve the survival and migration of NSCs grafted for stroke therapy. Functional peptide drugs, which could inhibit endogenous HIF-1𝜶 ubiquitination, might be used to effectively upregulate the HIF-1𝜶 expression in NSCs, thereby to improve the therapeutic effect in ischemia stroke. Herein, a magnetic resonance imaging (MRI)-visible nanomedicine is developed to codeliver functional peptides and superparamagnetic iron oxide (SPIO) nanoparticles into NSCs. This nanomedicine not only promotes the survival and migration ability of NSCs but also allows an in vivo tracking of transplanted NSCs with MRI. The results demonstrate the great potential of the functional peptides-complexed multifunctional nanomedicine in boosting the therapeutic effect of stem cell-based therapy in stroke.

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MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex

Abstract: Visual Abstract

Cited by 50 publications

References 62 publications

MANF Ablation Causes Prolonged Activation of the UPR without Neurodegeneration in the Mouse Midbrain Dopamine System

MANF Ablation Causes Prolonged Activation of the UPR without Neurodegeneration in the Mouse Midbrain Dopamine System

Cortical progenitor biology: key features mediating proliferation versus differentiation

Upregulating HIF‐1α to Boost the Survival of Neural Stem Cells via Functional Peptides‐Complexed MRI‐Visible Nanomedicine for Stroke Therapy

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