Neuron-specific expression of p48 Ebp1 during murine brain development and its contribution to CNS axon regeneration

Ko, Hyo Rim; Hwang, Inwoo; Ahn, So Yoon; Chang, Yun Sil; Park, Won Soon; Ahn, Jee-Yin

doi:10.5483/bmbrep.2017.50.3.190

Cited by 11 publications

(15 citation statements)

References 29 publications

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“…Few studies are available that provide in vivo evidence of EBP1 functions due to a lack of an appropriate mammalian model systems. We have previously demonstrated that p48 EBP1 is the major isoform in the developing brain neurons of rats and during murine brain development, whereas there is no detectable p42 EBP1 expression during the embryonic stage 4 , 27 . This also correlated with the ErbB3 expression profile, which is extremely limited in the developing CNS of mice.…”

Section: The Role Of P48 Ebp1 In Developmentmentioning

confidence: 99%

“…The longer form of p48 Ebp1 is the predominant form that is highly expressed in mammalian cells during embryogenesis and is maintained at a certain level after birth. p42 EBP1 can be detected after birth when the p48 EBP1 level is decreased relative to its level at the embryonic period 4 . In several types of cancer cells, including glioblastoma multiforme (GBM) and lung cancer cells, p48 EBP1 expression was notably high, which was noteworthy because of its oncogenic function.…”

Section: Introductionmentioning

confidence: 99%

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The roles of multifunctional protein ErbB3 binding protein 1 (EBP1) isoforms from development to disease

Hwang

Ahn

2020

Exp Mol Med

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The roles of the two isoforms of ErbB3-binding protein 1 (Ebp1) in cellular function and its regulation in disease and development is a stimulating area in current fields of biology, such as neuroscience, cancer biology, and structural biology. Over the last two decades, a growing body of studies suggests have suggested different functions for the EBP1 isoforms in various cancers, along with their specific binding partners in the ubiquitin-proteasome system. Owing to the specific cellular context or spatial/temporal expression of the EBP1 isoforms, either transcriptional repression or the activation function of EBP1 has been proposed, and epigenetic regulation by p48 EBP1 has also been observed during in the embryo development, including in brain development and neurologic disorders, such as schizophrenia, in using an Ebp1 knockout mouse model. Here, we review recent findings that have shaped our current understanding of the emerging function of EBP1 isoforms in cellular events and gene expression, from development to disease.

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Section: The Role Of P48 Ebp1 In Developmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The roles of multifunctional protein ErbB3 binding protein 1 (EBP1) isoforms from development to disease

Hwang

Ahn

2020

Exp Mol Med

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“…; Ko et al . ). EBP1 has active involvement of cell growth, apoptosis and differentiation in many cell types (Radomski & Jost ; Xia et al .…”

Section: Introductionmentioning

confidence: 97%

Ebp1 regulates myogenic differentiation of myoblast cells via SMAD2/3 signaling pathway

Wang

Liu

et al. 2017

Dev Growth Differ

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Regulation of skeletal muscle development requires many of the regulatory networks that are fundamental to developmental myogenesis. ErbB3 binding protein-1 (Ebp1) is involved in the control of myoblasts development in chicken. However, the expression and biological functions of Ebp1 in the progress of myogenesis are unclear. This study focused on determining the effect of Ebp1 on myogenic proliferation and differentiation using a primary myoblasts culture model. Ebp1 was found to upregulate in proliferating myoblasts and decrease at the early stage of myogenic differentiation. The level of endogenous Ebp1 increased from E9 to E20 chicken leg muscles. Knockdown of Ebp1 had no effect on myoblasts proliferation. However, myogenic differentiation into multinucleated myotubes was significantly reduced. The mRNA and protein expression of MRFs was decreased when Ebp1 was knocked down. Downregulation of Ebp1, accompanied by elevated levels of pSMAD2/3, suggests that Ebp1 is involved in regulating myogenic differentiation via SMAD2/3 inhibition. The phosphorylation of SMAD2/3 was activated and the expression of MYOD and MYOG was reduced in Ebp1 knockdown myoblasts, but addition of LY2109761 (an inhibitor specified to SMAD2/3) blocked these effects. Collectively, these results indicate that Ebp1 promotes myoblast differentiation by inhibition of SMAD2/3 signaling pathway during chicken myogenesis. These data provide new insights into the biological role of Ebp1 in embryonic chicken skeletal muscle development.

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“…EBP1 p48 isoform was found to be predominantly localized in neurons, rather than astrocyte, of the embryonic brain. EBP1 p42 expression was observed in mice after birth [8]. In the injured hippocampus, introduction of p48EBP1 by AAV2 delivery system resulted in notable regeneration of axon growth [8], implying that p48EBP1 may play an important role in processes of neural development and recovery.…”

Section: Introductionmentioning

confidence: 99%

“…EBP1 p42 expression was observed in mice after birth [8]. In the injured hippocampus, introduction of p48EBP1 by AAV2 delivery system resulted in notable regeneration of axon growth [8], implying that p48EBP1 may play an important role in processes of neural development and recovery. However, the physiological function of p48 EBP1 were not defined in developing brain tissues in vivo, because mammalian models of EBP1 deletion have not been developed.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Epigenetic Control Contributes to Schizophrenia-Like Behavior in Ebp1+/− Mice

Hwang

Ahn

2020

IJMS

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Dysregulation of epigenetic machinery can cause a variety of neurological disorders associated with cognitive abnormalities. In the hippocampus of postmortem Schizophrenia (SZ) patients, the most notable finding is the deregulation of GAD67 along with differential regulation of epigenetic factors associated with glutamate decarboxylase 67 (GAD67) expression. As we previously reported, ErbB3-binding protein 1 (EBP1) is a potent epigenetic regulator. EBP1 can induce repression of Dnmt1, a well-studied transcriptional repressor of GAD67. In this study, we investigated whether EBP1 contributes to the regulation of GAD67 expression in the hippocampus, controlling epigenetic machinery. In accordance with SZ-like behaviors in Ebp1 (+/−) mice, heterozygous deletion of EBP1 led to a dramatic reduction of GAD67 expression, reflecting an abnormally high level of Dnmt1. Moreover, we found that EBP1 binds to the promoter region of HDAC1, which leads to histone deacetylation of GAD67, and suppresses histone deacetylase 1 (HDAC1) expression, inversely mirroring an unusually high level of HDAC1 in Ebp1 (+/−) mice. However, EBP1 mutant (p.Glu 183 Ter) found in SZ patients did not elevate the expression of GAD67, failing to suppress Dnmt1 and/or HDAC1 expression. Therefore, this data supports the hypothesis that a reduced amount of EBP1 may contribute to an etiology of SZ due to a loss of transcriptional inhibition of epigenetic repressors, leading to a decreased expression of GAD67. Figure 1. Deficits in hippocampus development in Ebp1 (+/−) mice. (A) Ebp1 (+/+) and Ebp1 (+/−) 1 month and 958 month old mouse brains were isolated and subjected to Nissl staining (to compare the brain sizes 96 (upper)) or was stained with anti-ErbB3-binding protein 1 (EBP1) (red, marker for EBP1) and anti-97 NEUN (green, marker for neuronal cell) antibodies (to compare sizes of hippocampus (bottom)). The 98 whole brain size of Ebp1 (+/−) mouse was smaller than that of Ebp1 (+/+) for about 15%. Especially, the 99 hippocampus size was much smaller than that of Ebp1 (+/+) for about 30% 8 months after birth. Bar Representative images of the whole brain structure of Ebp1 (+/+) and Ebp1 (+/-) mouse are shown; coronal 102 (right) and transverse (left) T2-weighted images; MRI images of brain from 1 month (upper) or 8 103 month mice (bottom). Representative galleries of T2-weighted MRI images are shown. MRI was used 104 to determine the size of hippocampus. The hippocampus (light green) and cortex (light blue) are 106 hierarchical clustering of differentially expressed RNA of GABAergic neuron gene set was derived 107 using microarray of E12.5 Ebp1 deficient mouse brain samples. In the cluster heat map, red indicates 108 high relative gene expression and green indicates low relative gene expression. To confirm down 157 in hippocampus. (A) representative hippocampus structure is displayed. Created with BioRender. (B) 158 WT and Ebp1 heterozygous mouse brain were isolated and subjected to IHC staining with anti-EBP1 159 and TUJ1 antibodies, early neuronal marke...

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Neuron-specific expression of p48 Ebp1 during murine brain development and its contribution to CNS axon regeneration

Cited by 11 publications

References 29 publications

The roles of multifunctional protein ErbB3 binding protein 1 (EBP1) isoforms from development to disease

The roles of multifunctional protein ErbB3 binding protein 1 (EBP1) isoforms from development to disease

Ebp1 regulates myogenic differentiation of myoblast cells via SMAD2/3 signaling pathway

Dysregulation of Epigenetic Control Contributes to Schizophrenia-Like Behavior in Ebp1+/− Mice

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