APLP2 regulates neuronal stem cell differentiation during cortical development

Shariati, S. Ali M.; Lau, Pierre; Hassan, Bassem A.; Müller, Ulrike; Dotti, Carlos G.; Strooper, Bart De; Gartner, Agnès

doi:10.1242/jcs.122440

Cited by 44 publications

(26 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, RBM5 knockdown also increased APLP2-a key protein involved in cortical neuron development and synaptic function in adult mice. [29][30][31] This novel finding suggests that RBM5 may also regulate genes involved in neuronal function.…”

Section: Discussionmentioning

confidence: 82%

The Nuclear Splicing Factor RNA Binding Motif 5 Promotes Caspase Activation in Human Neuronal Cells, and Increases after Traumatic Brain Injury in Mice

Jackson

Janesko‐Feldman

et al. 2015

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Splicing factors (SFs) coordinate nuclear intron/exon splicing of RNA. Splicing factor disturbances can cause cell death. RNA binding motif 5 (RBM5) and 10 (RBM10) promote apoptosis in cancer cells by activating detrimental alternative splicing of key death/survival genes. The role(s) of RBM5/10 in neurons has not been established. Here, we report that RBM5 knockdown in human neuronal cells decreases caspase activation by staurosporine. In contrast, RBM10 knockdown augments caspase activation. To determine whether brain injury alters RBM signaling, we measured RBM5/10 protein in mouse cortical/hippocampus homogenates after controlled cortical impact (CCI) traumatic brain injury (TBI) plus hemorrhagic shock (CCI+HS). The RBM5/10 staining was higher 48 to 72 hours after injury and appeared to be increased in neuronal nuclei of the hippocampus. We also measured levels of other nuclear SFs known to be essential for cellular viability and report that splicing factor 1 (SF1) but not splicing factor 3A (SF3A) decreased 4 to 72 hours after injury. Finally, we confirm that RBM5/10 regulate protein expression of several target genes including caspase-2, cellular FLICE-like inhibitory protein (c-FLIP), LETM1 Domain-Containing Protein 1 (LETMD1), and amyloid precursor-like protein 2 (APLP2) in neuronal cells. Knockdown of RBM5 appeared to increase expression of c-FLIP(s), LETMD1, and APLP2 but decrease caspase-2.

show abstract

Section: Discussionmentioning

confidence: 82%

The Nuclear Splicing Factor RNA Binding Motif 5 Promotes Caspase Activation in Human Neuronal Cells, and Increases after Traumatic Brain Injury in Mice

Jackson

Janesko‐Feldman

et al. 2015

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…In utero electroporation was performed as described (Shariati et al, 2013). Pregnant mice were anaesthetized by intramuscular injections of 88 mg ketamine and 132 mg xylazine per gram of body weight.…”

Section: Methodsmentioning

confidence: 99%

Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling

Fazzari

Sabanov

et al. 2014

eLife

Self Cite

View full text Add to dashboard Cite

Neuregulin 1 (NRG1) and the γ-secretase subunit APH1B have been previously implicated as genetic risk factors for schizophrenia and schizophrenia relevant deficits have been observed in rodent models with loss of function mutations in either gene. Here we show that the Aph1b-γ-secretase is selectively involved in Nrg1 intracellular signalling. We found that Aph1b-deficient mice display a decrease in excitatory synaptic markers. Electrophysiological recordings show that Aph1b is required for excitatory synaptic transmission and plasticity. Furthermore, gain and loss of function and genetic rescue experiments indicate that Nrg1 intracellular signalling promotes dendritic spine formation downstream of Aph1b-γ-secretase in vitro and in vivo. In conclusion, our study sheds light on the physiological role of Aph1b-γ-secretase in brain and provides a new mechanistic perspective on the relevance of NRG1 processing in schizophrenia.DOI: http://dx.doi.org/10.7554/eLife.02196.001

show abstract

“…The pCAGFmr1 construct was obtained as follows: full-length Fmr1 mouse cDNA was inserted into the pCAGEN plasmid using the NotI and EcoRV restriction sites. The BLBP-EGFP plasmid was kindly provided by S.A. Shariati (KU Leuven) 52 . GFP-tagged N-cadherin cloned in pCAGG vector was kindly provided by C. Kalcheim (Hebrew University-Hadassah Medical School) 53 .…”

Section: Competing Financial Interestsmentioning

confidence: 99%

FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry

et al. 2014

Self Cite

View full text Add to dashboard Cite

Deficiencies in fragile X mental retardation protein (FMRP) are the most common cause of inherited intellectual disability, fragile X syndrome (FXS), with symptoms manifesting during infancy and early childhood. Using a mouse model for FXS, we found that Fmrp regulates the positioning of neurons in the cortical plate during embryonic development, affecting their multipolar-to-bipolar transition (MBT). We identified N-cadherin, which is crucial for MBT, as an Fmrp-regulated target in embryonic brain. Furthermore, spontaneous network activity and high-resolution brain imaging revealed defects in the establishment of neuronal networks at very early developmental stages, further confirmed by an unbalanced excitatory and inhibitory network. Finally, reintroduction of Fmrp or N-cadherin in the embryo normalized early postnatal neuron activity. Our findings highlight the critical role of Fmrp in the developing cerebral cortex and might explain some of the clinical features observed in patients with FXS, such as alterations in synaptic communication and neuronal network connectivity.

show abstract

APLP2 regulates neuronal stem cell differentiation during cortical development

Cited by 44 publications

References 49 publications

The Nuclear Splicing Factor RNA Binding Motif 5 Promotes Caspase Activation in Human Neuronal Cells, and Increases after Traumatic Brain Injury in Mice

The Nuclear Splicing Factor RNA Binding Motif 5 Promotes Caspase Activation in Human Neuronal Cells, and Increases after Traumatic Brain Injury in Mice

Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling

FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry

Contact Info

Product

Resources

About