ERBB3-mediated regulation of Bergmann glia proliferation in cerebellar lamination

Sathyamurthy, Anupama; Yin, Dong Min; Barik, Arnab; Shen, Chengyong; Bean, Jonathan C.; Figueiredo, Dwight; She, Jin Xiong; Xiong, Wen Cheng; Mei, Lin

doi:10.1242/dev.115931

Cited by 18 publications

(13 citation statements)

References 83 publications

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“…Cao et al 35 ) based largely on a report of reduced autophosphorylation compared to EGFR in insect cells with induced ErbB3 expression, 36 recent studies have suggested that ErbB3 has sufficient kinase activity for signaling, 37 , 38 , 39 and its downstream signaling primarily involves PI3K/AKT. 40 ErbB3 has also recently been found to be required for certain types of cell proliferation in the brain, likely due to downstream PI3K signaling. 40 Peripheral NRG1 administration (shown to be safe in humans 41 , 42 ) increases neurogenesis, producing additional GCs expressing ErbB3, with concomitant antidepressant-like effects.…”

Section: Discussionmentioning

confidence: 99%

Disrupted hippocampal neuregulin-1/ErbB3 signaling and dentate gyrus granule cell alterations in suicide

et al. 2017

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Neuregulin-1 (NRG1) and ErbB receptors have been associated with psychopathology, and NRG1-ErbB3 signaling has been shown to increase hippocampal neurogenesis and induce antidepressant-like effects. In this study, we aimed to determine whether deficits in NRG1 or ErbBs might be present in the hippocampus of suicide completers. In well-characterized postmortem hippocampal samples from suicides and matched sudden-death controls, we assessed gene expression and methylation using qRT-PCR and EpiTYPER, respectively. Moreover, in hippocampal tissues stained with cresyl violet, stereology was used to quantify numbers of granule cells and of glia. Granule cell body size was examined with a nucleator probe, and granule cell layer volume with a Cavalieri probe. Unmedicated suicides showed sharply decreased hippocampal ErbB3 expression and decreased numbers of ErbB3-expressing granule cell neurons in the anterior dentate gyrus; a phenomenon seemingly reversed by antidepressant treatment. Furthermore, we found ErbB3 expression to be significantly decreased in the dentate gyrus of adult mice exposed to chronic social defeat stress. Taken together, these results reveal novel suicidal endophenotypes in the hippocampus, as well as a putative etiological mechanism underlying suicidality, and suggest that antidepressant or NRG1 treatment may reverse a potential deficit in anterior dentate gyrus granule cell neurons in individuals at risk of dying by suicide.

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Section: Discussionmentioning

confidence: 99%

Disrupted hippocampal neuregulin-1/ErbB3 signaling and dentate gyrus granule cell alterations in suicide

et al. 2017

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“…S9). Because BG radial fibers provide scaffolds for GNP migration (36,42), the abnormal BG morphology and localization likely contribute to the impaired migration of GNPs and morphogenesis defects in hGFAP-Cre;Rack1 F/F mice. hGFAP-Cre and Atoh1-Cre mice, but not GLAST-CreER T2 -driven Rack1 conditional KO mice, display abnormal BG morphology.…”

Section: Ablation Of Rack1 In Multipotent Nscs Disrupts Cerebellarmentioning

confidence: 99%

Opposite regulation of Wnt/β-catenin and Shh signaling pathways by Rack1 controls mammalian cerebellar development

Yang

Zhu

Cheng

et al. 2019

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

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The development of the cerebellum depends on intricate processes of neurogenesis, migration, and differentiation of neural stem cells (NSCs) and progenitor cells. Defective cerebellar development often results in motor dysfunctions and psychiatric disorders. Understanding the molecular mechanisms that underlie the complex development of the cerebellum will facilitate the development of novel treatment options. Here, we report that the receptor for activated C kinase (Rack1), a multifaceted signaling adaptor protein, regulates mammalian cerebellar development in a cell type-specific manner. Selective deletion of Rack1 in mouse NSCs or granule neuron progenitors (GNPs), but not Bergmann glial cells (BGs), causes severe defects in cerebellar morphogenesis, including impaired folia and fissure formation. NSCs and GNPs lacking Rack1 exhibit enhanced Wnt/β-catenin signaling but reduced Sonic hedgehog (Shh) signaling. Simultaneous deletion of β-catenin in NSCs, but not GNPs, significantly rescues theRack1mutant phenotype. Interestingly, Rack1 controls the activation of Shh signaling by regulating the ubiquitylation and stability of histone deacetylase 1 (HDAC1)/HDAC2. Suppression of HDAC1/HDAC2 activity in the developing cerebellum phenocopies theRack1mutant. Together, these results reveal a previously unknown role of Rack1 in controlling mammalian cerebellar development by opposite regulation of Wnt/β-catenin and Shh signaling pathways.

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“…Proliferation and migration of neural progenitor cells in the external granular layer (EGL) as well as the proliferation of immature glial cells are characteristic of late fetal and early postnatal development of the cerebellum. All of these processes are largely influenced or directed by the activity of the Purkinje cells [11][12][13] together with Bergmann Glia [14][15][16], by glia-glia [17][18][19], as well as by glia-neuron interactions [20][21][22], mainly through signaling via growth factors, chemokines and cytokines, transmitters and transcription factors. This review seeks to highlight shared mechanisms of glial cell regulation that are relevant for development and disease of the cerebellar white matter that may serve to design future strategies for protection.…”

Section: Introductionmentioning

confidence: 99%

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

et al. 2020

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The cerebellum is a brain region that undergoes extremely dynamic growth during perinatal and postnatal development which is regulated by the proper interaction between glial cells and neurons with a complex concert of growth factors, chemokines, cytokines, neurotransmitters and transcriptions factors. The relevance of cerebellar functions for not only motor performance but also for cognition, emotion, memory and attention is increasingly being recognized and acknowledged. Since perturbed circuitry of cerebro-cerebellar trajectories can play a role in many central nervous system pathologies and thereby contribute to neurological symptoms in distinct neurodevelopmental and neurodegenerative diseases, is it the aim with this mini-review to highlight the pathways of glia-glia interplay being involved. The designs of future treatment strategies may hence be targeted to molecular pathways also playing a role in development and disease of the cerebellum.

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ERBB3-mediated regulation of Bergmann glia proliferation in cerebellar lamination

Cited by 18 publications

References 83 publications

Disrupted hippocampal neuregulin-1/ErbB3 signaling and dentate gyrus granule cell alterations in suicide

Disrupted hippocampal neuregulin-1/ErbB3 signaling and dentate gyrus granule cell alterations in suicide

Opposite regulation of Wnt/β-catenin and Shh signaling pathways by Rack1 controls mammalian cerebellar development

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

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