Neuronal Subtypes Are Specified by the Level of<i>neurod</i>Expression in the Zebrafish Lateral Line

Sato, Akira; Takeda, Hiroyuki

doi:10.1523/jneurosci.4568-12.2013

Cited by 14 publications

(13 citation statements)

References 33 publications

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“…Specifically, elevated Neurod expression increases the number of glucagon-expressing cells but decreases the number of insulin-expressing cells. A similar role has recently been reported for differential levels of Neurod within the developing zebrafish posterior lateral line (PLL) (Sato and Takeda, 2013). In this group of migrating neurons there are two classes of cells, leaders and followers, which express high and low levels of Neurod protein, respectively.…”

Section: Discussionsupporting

confidence: 78%

“…In this group of migrating neurons there are two classes of cells, leaders and followers, which express high and low levels of Neurod protein, respectively. Overexpression of Neurod in a single PLL neuron precursor is sufficient to promote its differentiation into the leader cell type (Sato and Takeda, 2013). Our immunohistochemistry has shown that the individual cells of the dorsal endocrine pancreatic bud similarly display heterogeneous Neurod protein levels (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

Dalgin

Prince

2015

Developmental Biology

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During development a network of transcription factors functions to differentiate foregut cells into pancreatic endocrine cells. Differentiation of appropriate numbers of each hormone-expressing endocrine cell type is essential for the normal development of the pancreas and ultimately for effective maintenance of blood glucose levels. A fuller understanding of the details of endocrine cell differentiation may contribute to development of cell replacement therapies to treat diabetes. In this study, by using morpholino and gRNA/Cas9 mediated knockdown we establish that differential levels of the basic-helix loop helix (bHLH) transcription factor Neurod are required for the differentiation of distinct endocrine cell types in developing zebrafish. While Neurod plays a role in the differentiation of all endocrine cells, we find that differentiation of glucagon-expressing alpha cells is disrupted by a minor reduction in Neurod levels, whereas differentiation of insulin-expressing beta cells is less sensitive to Neurod depletion. The endocrine cells that arise during embryonic stages to produce the primary islet, and those that arise subsequently during larval stages from the intra-pancreatic duct (IPD) to ultimately contribute to the secondary islets, show similar dependence on differential Neurod levels. Intriguingly, Neurod-deficiency triggers premature formation of endocrine precursors from the IPD during early larval stages. However, the Neurod-deficient endocrine precursors fail to differentiate appropriately, and the larvae are unable to maintain normal glucose levels. In summary, differential levels of Neurod are required to generate endocrine pancreas subtypes from precursors during both embryonic and larval stages, and Neurod function is in turn critical to endocrine function.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

Dalgin

Prince

2015

Developmental Biology

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“…Neurod1 gene is specifically expressed during central nervous system development in zebrafish and is a key differentiation factor during neurogenesis; it is also involved in the determination of neural subtypes in the ganglia24. At 48 hpf the expression of neurod1 is more specifically localized at tegmentum, diencephalon, hindbrain and lateral line gaglia2526. The vast majority of coasy morphants (85%, n = 45/53) showed altered neurod1 expression.…”

Section: Resultsmentioning

confidence: 99%

Down-regulation of coasy, the gene associated with NBIA-VI, reduces Bmp signaling, perturbs dorso-ventral patterning and alters neuronal development in zebrafish

Khatri

Zizioli

Tiso

et al. 2016

Sci Rep

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Mutations in Pantothenate kinase 2 and Coenzyme A (CoA) synthase (COASY), genes involved in CoA biosynthesis, are associated with rare neurodegenerative disorders with brain iron accumulation. We showed that zebrafish pank2 gene plays an essential role in brain and vasculature development. Now we extended our study to coasy. The gene has high level of sequence identity with the human ortholog and is ubiquitously expressed from the earliest stages of development. The abrogation of its expression led to strong reduction of CoA content, high lethality and a phenotype resembling to that of dorsalized mutants. Lower doses of morpholino resulted in a milder phenotype, with evident perturbation in neurogenesis and formation of vascular arborization; the dorso-ventral patterning was severely affected, the expression of bone morphogenetic protein (Bmp) receptors and activity were decreased, while cell death increased. These features specifically correlated with the block in CoA biosynthesis and were rescued by the addition of CoA to fish water and the overexpression of the human wild-type, but not mutant gene. These results confirm the absolute requirement for adequate levels of CoA for proper neural and vascular development in zebrafish and point to the Bmp pathway as a possible molecular connection underlining the observed phenotype.

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“…The afferent neurons of the pLL ganglion are heterogeneous and have been classified into at least two types. The leader neurons (or type A) are the first to differentiate, are characterized by a large soma and are distributed throughout the entire ganglion [ 27 , 43 , 46 ]. The peripheral axonal projections of these neurons comigrate with the primordium and innervate the primary neuromasts [ 43 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

Axon-Schwann cell interactions during peripheral nerve regeneration in zebrafish larvae

et al. 2014

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BackgroundPeripheral nerve injuries can severely affect the way that animals perceive signals from the surrounding environment. While damage to peripheral axons generally has a better outcome than injuries to central nervous system axons, it is currently unknown how neurons re-establish their target innervations to recover function after injury, and how accessory cells contribute to this task. Here we use a simple technique to create reproducible and localized injury in the posterior lateral line (pLL) nerve of zebrafish and follow the fate of both neurons and Schwann cells.ResultsUsing pLL single axon labeling by transient transgene expression, as well as transplantation of glial precursor cells in zebrafish larvae, we individualize different components in this system and characterize their cellular behaviors during the regenerative process. Neurectomy is followed by loss of Schwann cell differentiation markers that is reverted after nerve regrowth. We show that reinnervation of lateral line hair cells in neuromasts during pLL nerve regeneration is a highly dynamic process with promiscuous yet non-random target recognition. Furthermore, Schwann cells are required for directional extension and fasciculation of the regenerating nerve. We provide evidence that these cells and regrowing axons are mutually dependant during early stages of nerve regeneration in the pLL. The role of ErbB signaling in this context is also explored.ConclusionThe accessibility of the pLL nerve and the availability of transgenic lines that label this structure and their synaptic targets provides an outstanding in vivo model to study the different events associated with axonal extension, target reinnervation, and the complex cellular interactions between glial cells and injured axons during nerve regeneration.

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Neuronal Subtypes Are Specified by the Level ofneurodExpression in the Zebrafish Lateral Line

Cited by 14 publications

References 33 publications

Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

Down-regulation of coasy, the gene associated with NBIA-VI, reduces Bmp signaling, perturbs dorso-ventral patterning and alters neuronal development in zebrafish

Axon-Schwann cell interactions during peripheral nerve regeneration in zebrafish larvae

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