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An exon junction complex-independent function of Barentsz in neuromuscular synapse growth

ABSTRACT: The exon junction complex controls the translation, degradation and localization of spliced mRNAs, and three of its core subunits also play a role in splicing. Here we show that a fourth subunit, Barentsz, has distinct functions within and separate from the exon junction complex in Drosophila neuromuscular development. The distribution of mitochondria in larval muscles requires Barentsz as well as other exon junction complex subunits, and is not rescued by a Barentsz transgene in which residues required for binding to the core subunit eIF4AIII are mutated. In contrast, interactions with the exon junction complex are not required for Barentsz to promote the growth of neuromuscular synapses. We find that the Activin ligand Dawdle shows reduced expression in barentsz mutants and acts downstream of Barentsz to control synapse growth. Both barentsz and dawdle are required in motor neurons, muscles and glia for normal synapse growth, and exogenous Dawdle can rescue synapse growth in the absence of barentsz. These results identify a biological function for Barentsz that is independent of the exon junction complex.

SUBMITTER: Dr. Cheuk, Hei Ho

PROVIDER: S-SCDT-EMBOR-2021-53231V1 | biostudies-other |

REPOSITORIES: biostudies-other

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An exon junction complex-independent function of Barentsz in neuromuscular synapse growth.

Project description:The exon junction complex controls the translation, degradation, and localization of spliced mRNAs, and three of its core subunits also play a role in splicing. Here, we show that a fourth subunit, Barentsz, has distinct functions within and separate from the exon junction complex in Drosophila neuromuscular development. The distribution of mitochondria in larval muscles requires Barentsz as well as other exon junction complex subunits and is not rescued by a Barentsz transgene in which residues required for binding to the core subunit eIF4AIII are mutated. In contrast, interactions with the exon junction complex are not required for Barentsz to promote the growth of neuromuscular synapses. We find that the Activin ligand Dawdle shows reduced expression in barentsz mutants and acts downstream of Barentsz to control synapse growth. Both barentsz and dawdle are required in motor neurons, muscles, and glia for normal synapse growth, and exogenous Dawdle can rescue synapse growth in the absence of barentsz. These results identify a biological function for Barentsz that is independent of the exon junction complex.

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Neuromuscular Junction

Project description:NMJ Junction various time points normal C57BL10 LCM mRNA Keywords: other

2005-03-10 | GSE2394 | GEO

The Extracellular and Cytoplasmic Domains of Syndecan Cooperate Postsynaptically to Promote Synapse Growth at the Drosophila Neuromuscular Junction.

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The PDZ-GEF Gef26 regulates synapse development and function via FasII and Rap1 at the Drosophila neuromuscular junction.

Project description:Guanine nucleotide exchange factors (GEFs) are essential for small G proteins to activate their downstream signaling pathways, which are involved in morphogenesis, cell adhesion, and migration. Mutants of Gef26, a PDZ-GEF (PDZ domain-containing guanine nucleotide exchange factor) in Drosophila, exhibit strong defects in wings, eyes, and the reproductive and nervous systems. However, the precise roles of Gef26 in development remain unclear. In the present study, we analyzed the role of Gef26 in synaptic development and function. We identified significant decreases in bouton number and branch length at larval neuromuscular junctions (NMJs) in Gef26 mutants, and these defects were fully rescued by restoring Gef26 expression, indicating that Gef26 plays an important role in NMJ morphogenesis. In addition to the observed defects in NMJ morphology, electrophysiological analyses revealed functional defects at NMJs, and locomotor deficiency appeared in Gef26 mutant larvae. Furthermore, Gef26 regulated NMJ morphogenesis by regulating the level of synaptic Fasciclin II (FasII), a well-studied cell adhesion molecule that functions in NMJ development and remodeling. Finally, our data demonstrate that Gef26-specific small G protein Rap1 worked downstream of Gef26 to regulate the level of FasII at NMJs, possibly through a βPS integrin-mediated signaling pathway. Taken together, our findings define a novel role of Gef26 in regulating NMJ development and function.

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Exon array data from neuromuscular junction (NMJ) in mouse skeletal muscle.

Project description:The RNA from NMJ and non-NMJs samples were examined using microarray analysis with of identifying novel regulatory genes that are preferentially expressed in the synaptic regions of the isolated muscle fibers.

2019-12-12 | GSE92400 | GEO

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Project description:The formation of the nervous system requires a balance between proliferation, differentiation, and migration of neural progenitors (NPs). Mutations in genes regulating development impede neurogenesis and lead to neuropsychiatric diseases, including autism spectrum disorders (ASDs) and schizophrenia (SZ). Recently, mutations in nonsense-mediated mRNA decay genes have been associated with ASDs, intellectual disability (ID), and SZ. Here, we examine the function of a gene in the exon junction complex, Rbm8a, in the cortical development. When Rbm8a is selectively knocked out in neural stem cells, the resulting mice exhibit microcephaly, early postnatal lethality, and altered distribution of excitatory neurons in the neocortex. Moreover, Rbm8a haploinsufficiency in the central nervous system decreases cell proliferation in the ganglionic eminences. Parvalbumin+ and neuropeptide Y+ interneurons in the cortex are significantly reduced, and distribution of interneurons are altered. Consistently, neurons in the cortex of conditional knockout (cKO) mice show a significant decrease in GABA frequency. Transcriptomic analysis revealed differentially expressed genes enriched in telencephalon development and mitosis. To further investigate the role of Rbm8a in interneuron differentiation, conditional KO of Rbm8a in NKX2.1 interneuron progenitor cells reduces progenitor proliferation and alters interneuron distributions. Taken together, these data reveal a critical role of Rbm8a in interneuron development, and establish that perturbation of this gene leads to profound cortical deficits.

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