A new mode of pancreatic islet innervation revealed by live imaging in zebrafish

Pancreatic islets are innervated by autonomic and sensory nerves that influence their function. Analyzing the innervation process should provide insight into the nerve-endocrine interactions and their roles in development and disease. Here, using in vivo time-lapse imaging and genetic analyses in zebrafish, we determined the events leading to islet innervation. Comparable neural density in the absence of vasculature indicates that it is dispensable for early pancreatic innervation. Neural crest cells are in close contact with endocrine cells early in development. We find these cells give rise to neurons that extend axons toward the islet as they surprisingly migrate away. Specific ablation of these neurons partly prevents other neurons from migrating away from the islet resulting in diminished innervation. Thus, our studies establish the zebrafish as a model to interrogate mechanisms of organ innervation, and reveal a novel mode of innervation whereby neurons establish connections with their targets before migrating away.

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Pancreatic Islets Communicate With the Brain via Vagal Sensory Neurons

10.1101/780395 ◽

2019 ◽

Author(s):

Madina Makhmutova ◽

Jonathan Weitz ◽

Alejandro Tamayo ◽

Elizabeth Pereira ◽

Joana Almaça ◽

...

Keyword(s):

Pancreatic Islets ◽

Beta Cells ◽

Sensory Neurons ◽

Pancreatic Islet ◽

Serotonin Receptor ◽

Sensory Nerves ◽

Sensory Axons ◽

Serotonin Signaling ◽

The Brain

SUMMARYDepleting visceral sensory nerves affects pancreatic islet function, glucose metabolism and diabetes onset, but how islet endocrine cells interact with sensory neurons has not been studied. Here we show that the pancreatic islet is innervated by vagal sensory axons expressing substance P, calcitonin-gene related peptide, and serotonin receptor 5HT3R. Vagal neurons projecting to the pancreas terminate in the commissural nucleus of the solitary tract. These neurons respond to chemical but not mechanical stimulation of the pancreas. By recording activity from nodose neurons in vivo and from sensory axons in living pancreas slices, we show that sensory nerves respond to serotonin secreted from stimulated beta cells. Serotonin is co-released with insulin and therefore conveys information about the secretory state of beta cells via vagal afferent nerves. Our study thus establishes that pancreatic islets communicate with the brain using the neural route and identifies serotonin signaling as a peripheral transduction mechanism.

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In vivo time-lapse imaging reveals extensive neural crest and endothelial cell interactions during neural crest migration and formation of the dorsal root and sympathetic ganglia

Developmental Biology ◽

10.1016/j.ydbio.2016.02.028 ◽

2016 ◽

Vol 413 (1) ◽

pp. 70-85 ◽

Cited By ~ 9

Author(s):

Lynn George ◽

Haley Dunkel ◽

Barbara J. Hunnicutt ◽

Michael Filla ◽

Charles Little ◽

...

Keyword(s):

Endothelial Cell ◽

Neural Crest ◽

Dorsal Root ◽

Time Lapse ◽

Sympathetic Ganglia ◽

Cell Interactions ◽

Time Lapse Imaging ◽

Neural Crest Migration

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Topical Review: Neuronal Migration in Cortical Development

Journal of Child Neurology ◽

10.1177/08830738040190030201 ◽

2004 ◽

Vol 19 (3) ◽

pp. 274-279

Author(s):

Shigeaki Kanatani ◽

Hidenori Tabata ◽

Kazunori Nakajima

Keyword(s):

Neuronal Migration ◽

Radial Glia ◽

Asymmetric Cell Division ◽

Time Lapse ◽

Radial Glial Cells ◽

Daughter Cells ◽

Radial Glial ◽

Time Lapse Imaging ◽

Mitotic Behavior

Cortical formation in the developing brain is a highly complicated process involving neuronal production (through symmetric or asymmetric cell division) interaction of radial glia with neuronal migration, and multiple modes of neuronal migration. It has been convincingly demonstrated by numerous studies that radial glial cells are neural stem cells. However, the processes by which neurons arise from radial glia and migrate to their final destinations in vivo are not yet fully understood. Recent studies using time-lapse imaging of neuronal migration are giving investigators an increasingly more detailed understanding of the mitotic behavior of radial glia and the migrating behavior of their daughter cells. In this review, we describe recent progress in elucidating neuronal migration in brain formation and how neuronal migration is disturbed by mutations in genes that control this process. ( J Child Neurol 2005;20:274—279).

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Individual neuronal subtypes control initial myelin sheath growth and stabilization

Neural Development ◽

10.1186/s13064-020-00149-3 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Heather N. Nelson ◽

Anthony J. Treichel ◽

Erin N. Eggum ◽

Madeline R. Martell ◽

Amanda J. Kaiser ◽

...

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Myelin Sheath ◽

Time Lapse ◽

Marked Individual ◽

Larval Zebrafish ◽

Sheath Formation ◽

Time Lapse Imaging

Abstract Background In the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Some contacts stabilize, leading to the initiation of axon wrapping, nascent myelin sheath formation, concentric wrapping and sheath elongation, and sheath stabilization or pruning by oligodendrocytes. Although axonal signals influence the overall process of myelination, the precise oligodendrocyte behaviors that require signaling from axons are not completely understood. In this study, we investigated whether oligodendrocyte behaviors during the early events of myelination are mediated by an oligodendrocyte-intrinsic myelination program or are over-ridden by axonal factors. Methods To address this, we utilized in vivo time-lapse imaging in embryonic and larval zebrafish spinal cord during the initial hours and days of axon wrapping and myelination. Transgenic reporter lines marked individual axon subtypes or oligodendrocyte membranes. Results In the larval zebrafish spinal cord, individual axon subtypes supported distinct nascent sheath growth rates and stabilization frequencies. Oligodendrocytes ensheathed individual axon subtypes at different rates during a two-day period after initial axon wrapping. When descending reticulospinal axons were ablated, local spinal axons supported a constant ensheathment rate despite the increased ratio of oligodendrocytes to target axons. Conclusion We conclude that properties of individual axon subtypes instruct oligodendrocyte behaviors during initial stages of myelination by differentially controlling nascent sheath growth and stabilization.

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In Vivo Time-Lapse Imaging of Neuronal Development inXenopus

Cold Spring Harbor Protocols ◽

10.1101/pdb.top077156 ◽

2013 ◽

Vol 2013 (9) ◽

pp. pdb.top077156 ◽

Cited By ~ 4

Author(s):

Edward S. Ruthazer ◽

Anne Schohl ◽

Neil Schwartz ◽

Aydin Tavakoli ◽

Marc Tremblay ◽

...

Keyword(s):

Neuronal Development ◽

Time Lapse ◽

Time Lapse Imaging

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In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis

Development ◽

10.1242/dev.158477 ◽

2018 ◽

Vol 145 (3) ◽

pp. dev158477 ◽

Cited By ~ 7

Author(s):

Julia Freudenblum ◽

José A. Iglesias ◽

Martin Hermann ◽

Tanja Walsen ◽

Armin Wilfinger ◽

...

Keyword(s):

Pancreatic Islet ◽

In Vivo Imaging ◽

Endocrine Cells

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Examining seizure-induced effects on the dendritic growth of immature neurons, using in vivo time-lapse imaging of the intact juvenile brain

Clinical Neurophysiology ◽

10.1016/j.clinph.2007.03.028 ◽

2007 ◽

Vol 118 (7) ◽

pp. e186

Author(s):

D. Sesath Hewapathirane ◽

Simon Chen ◽

Wesley Yen ◽

Kurt Haas

Keyword(s):

Dendritic Growth ◽

Time Lapse ◽

Immature Neurons ◽

Time Lapse Imaging

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Sindbis Virus-Induced Neuronal Death Is both Necrotic and Apoptotic and Is Ameliorated byN-Methyl-d-Aspartate Receptor Antagonists

Journal of Virology ◽

10.1128/jvi.75.15.7114-7121.2001 ◽

2001 ◽

Vol 75 (15) ◽

pp. 7114-7121 ◽

Cited By ~ 70

Author(s):

Jennifer L. Nargi-Aizenman ◽

Diane E. Griffin

Keyword(s):

Cell Death ◽

Cortical Neurons ◽

Sindbis Virus ◽

Apoptotic Cell ◽

Time Lapse ◽

Apoptotic Cell Death ◽

Time Lapse Imaging ◽

Alphavirus Infection

ABSTRACT Virus infection of neurons leads to different outcomes ranging from latent and noncytolytic infection to cell death. Viruses kill neurons directly by inducing either apoptosis or necrosis or indirectly as a result of the host immune response. Sindbis virus (SV) is an alphavirus that induces apoptotic cell death both in vitro and in vivo. However, apoptotic changes are not always evident in neurons induced to die by alphavirus infection. Time lapse imaging revealed that SV-infected primary cortical neurons exhibited both apoptotic and necrotic morphological features and that uninfected neurons in the cultures also died. Antagonists of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors protected neurons from SV-induced death without affecting virus replication or SV-induced apoptotic cell death. These results provide evidence that SV infection activates neurotoxic pathways that result in aberrant NMDA receptor stimulation and damage to infected and uninfected neurons.

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