Probabilistic Splicing of Dscam1 Establishes Identity at the Level of Single Neurons

Miura, Satoru K.; Martins, André L.; Zhang, Kelvin X.; Graveley, Brenton R.; Zipursky, S. Lawrence

doi:10.1016/j.cell.2013.10.018

Cited by 86 publications

(95 citation statements)

References 35 publications

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“…The Drosophila mushroom body (MB), which forms bilaterally symmetric and dorsomedially bifurcated axonal lobe structures in the central brain, has been well studied as a model of neuronal development (Awasaki et al, 2011;Ito et al, 1997;Miura et al, 2013;Zhu et al, 2006). Among various regulators of neuronal morphogenesis, ADF/Cofilin and Rac GTPase (Rac) are key molecules in controlling cytoskeletal remodeling in axonal development (Bernstein and Bamburg, 2010;Hakeda-Suzuki et al, 2002;Hall and Lalli, 2010;Ono, 2007).…”

Section: Introductionmentioning

confidence: 99%

The NAV2 homolog Sickie regulates F-actin-mediated axonal growth inDrosophilamushroom body neurons via the non-canonical Rac-Cofilin pathway

et al. 2014

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The Rac-Cofilin pathway is essential for cytoskeletal remodeling to control axonal development. Rac signals through the canonical RacPak-LIMK pathway to suppress Cofilin-dependent axonal growth and through a Pak-independent non-canonical pathway to promote outgrowth. Whether this non-canonical pathway converges to promote Cofilin-dependent F-actin reorganization in axonal growth remains elusive. We demonstrate that Sickie, a homolog of the human microtubule-associated protein neuron navigator 2, cellautonomously regulates axonal growth of Drosophila mushroom body (MB) neurons via the non-canonical pathway. Sickie was prominently expressed in the newborn F-actin-rich axons of MB neurons. A sickie mutant exhibited axonal growth defects, and its phenotypes were rescued by exogenous expression of Sickie. We observed phenotypic similarities and genetic interactions among sickie and Rac-Cofilin signaling components. Using the MARCM technique, distinct F-actin and phospho-Cofilin patterns were detected in developing axons mutant for sickie and Rac-Cofilin signaling regulators. The upregulation of Cofilin function alleviated the axonal defect of the sickie mutant. Epistasis analyses revealed that Sickie suppresses the LIMK overexpression phenotype and is required for Pak-independent Rac1 and Slingshot phosphatase to counteract LIMK. We propose that Sickie regulates F-actin-mediated axonal growth via the non-canonical Rac-Cofilin pathway in a Slingshot-dependent manner.

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Section: Introductionmentioning

confidence: 99%

The NAV2 homolog Sickie regulates F-actin-mediated axonal growth inDrosophilamushroom body neurons via the non-canonical Rac-Cofilin pathway

et al. 2014

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“…The in vivo expression of each of the 12 exon 4 variants from the endogenous Dscam1 locus was visualized using distinct splicing reporters (Miura et al, 2013). The choice of an exon 4 variant was found to be different for neurons belonging to the same class and for neurons located in similar positions in individual animals.…”

Section: Neurexin Proteinsmentioning

confidence: 99%

Alternative Splicing in the Mammalian Nervous System: Recent Insights into Mechanisms and Functional Roles

Raj

Blencowe

2015

Neuron

404

392

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High-throughput transcriptomic profiling approaches have revealed that alternative splicing (AS) of precursor mRNAs, a fundamental process by which cells expand their transcriptomic diversity, is particularly widespread in the nervous system. AS events detected in the brain are more highly conserved than those detected in other tissues, suggesting that they more often provide conserved functions. Our understanding of the mechanisms and functions of neural AS events has significantly advanced with the coupling of various computational and experimental approaches. These studies indicate that dynamic regulation of AS in the nervous system is critical for modulating protein-protein interactions, transcription networks, and multiple aspects of neuronal development. Furthermore, several underappreciated classes of AS with the aforementioned roles in neuronal cells have emerged from unbiased, global approaches. Collectively, these findings emphasize the importance of characterizing neural AS in order to gain new insight into pathways that may be altered in neurological diseases and disorders.

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“…Fly Dscam1 Moreover, introducing a splice reporter into the Dscam1 locus showed that each neuron expresses multiple splice variants and that alternate exon selection was random from cell to cell regardless of type, lineage, and animal (Miura et al 2013). For Pcdhs, expression of each variable exon is controlled by its upstream promoter (Tasic et al 2002, Toyoda et al 2014, Wang et al 2002a).…”

Section: Figurementioning

confidence: 99%

Development of Dendritic Form and Function

Lefebvre¹,

Sanes

Kay

2015

Annu. Rev. Cell Dev. Biol.

200

207

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The nervous system is populated by numerous types of neurons, each bearing a dendritic arbor with a characteristic morphology. These type-specific features influence many aspects of a neuron's function, including the number and identity of presynaptic inputs and how inputs are integrated to determine firing properties. Here, we review the mechanisms that regulate the construction of cell type-specific dendrite patterns during development. We focus on four aspects of dendrite patterning that are particularly important in determining the function of the mature neuron: (a) dendrite shape, including branching pattern and geometry of the arbor; (b) dendritic arbor size;

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Probabilistic Splicing of Dscam1 Establishes Identity at the Level of Single Neurons

Cited by 86 publications

References 35 publications

The NAV2 homolog Sickie regulates F-actin-mediated axonal growth inDrosophilamushroom body neurons via the non-canonical Rac-Cofilin pathway

The NAV2 homolog Sickie regulates F-actin-mediated axonal growth inDrosophilamushroom body neurons via the non-canonical Rac-Cofilin pathway

Alternative Splicing in the Mammalian Nervous System: Recent Insights into Mechanisms and Functional Roles

Development of Dendritic Form and Function

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