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Article ; Online: Development and regeneration of the vagus nerve.

Isabella, Adam J / Moens, Cecilia B

Seminars in cell & developmental biology

2023 Volume 156, Page(s) 219–227

Abstract: The vagus nerve, with its myriad constituent axon branches and innervation targets, has long been a model of anatomical complexity in the nervous system. The branched architecture of the vagus nerve is now appreciated to be highly organized around the ... ...

Abstract	The vagus nerve, with its myriad constituent axon branches and innervation targets, has long been a model of anatomical complexity in the nervous system. The branched architecture of the vagus nerve is now appreciated to be highly organized around the topographic and/or molecular identities of the neurons that innervate each target tissue. However, we are only just beginning to understand the developmental mechanisms by which heterogeneous vagus neuron identity is specified, patterned, and used to guide the axons of particular neurons to particular targets. Here, we summarize our current understanding of the complex topographic and molecular organization of the vagus nerve, the developmental basis of neuron specification and patterned axon guidance that supports this organization, and the regenerative mechanisms that promote, or inhibit, the restoration of vagus nerve organization after nerve damage. Finally, we highlight key unanswered questions in these areas and discuss potential strategies to address these questions.
MeSH term(s)	Neurons/physiology ; Axons/physiology ; Vagus Nerve ; Nerve Regeneration
Language	English
Publishing date	2023-08-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2023.07.008
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Article: Position-independent functional refinement within the vagus motor topographic map.

Kaneko, Takuya / Boulanger-Weill, Jonathan / Isabella, Adam J / Moens, Cecilia B

bioRxiv : the preprint server for biology

2024

Abstract: Motor neurons in the central nervous system often lie in a continuous topographic map, where neurons that innervate different body parts are spatially intermingled. This is the case for the efferent neurons of the vagus nerve, which innervate diverse ... ...

Abstract	Motor neurons in the central nervous system often lie in a continuous topographic map, where neurons that innervate different body parts are spatially intermingled. This is the case for the efferent neurons of the vagus nerve, which innervate diverse muscle and organ targets in the head and viscera for brain-body communication. It remains elusive how neighboring motor neurons with different fixed peripheral axon targets develop the separate somatodendritic (input) connectivity they need to generate spatially precise body control. Here we show that vagus motor neurons in the zebrafish indeed generate spatially appropriate peripheral responses to focal sensory stimulation even when they are transplanted into ectopic positions within the topographic map, indicating that circuit refinement occurs after the establishment of coarse topography. Refinement depends on motor neuron synaptic transmission, suggesting that an experience-dependent periphery-to-brain feedback mechanism establishes specific input connectivity amongst intermingled motor populations.
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.11.557289
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Article ; Online: Mouse B2 SINE elements function as IFN-inducible enhancers

Isabella Horton / Conor J Kelly / Adam Dziulko / David M Simpson / Edward B Chuong

eLife, Vol

2023 Volume 12

Abstract: Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance ... ...

Abstract	Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an enhancer driving IFN-inducible expression of Dicer1. The rodent-specific B2 SINE family is highly abundant in the mouse genome and elements have been previously characterized to exhibit promoter, insulator, and non-coding RNA activity. Our work establishes a new role for B2 elements as inducible enhancer elements that influence mouse immunity, and exemplifies how lineage-specific TEs can facilitate evolutionary turnover and divergence of innate immune regulatory networks.
Keywords	interferon ; transposon ; gene regulation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mouse B2 SINE elements function as IFN-inducible enhancers.

Horton, Isabella / Kelly, Conor J / Dziulko, Adam / Simpson, David M / Chuong, Edward B

eLife

2023 Volume 12

Abstract	Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an enhancer driving IFN-inducible expression of
MeSH term(s)	Animals ; Mice ; Regulatory Sequences, Nucleic Acid ; Promoter Regions, Genetic ; Interferon-gamma/genetics ; Biological Evolution ; Binding Sites ; DNA Transposable Elements ; Enhancer Elements, Genetic/genetics
Chemical Substances	Interferon-gamma (82115-62-6) ; DNA Transposable Elements
Language	English
Publishing date	2023-05-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.82617
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Article ; Online: Intrinsic positional memory guides target-specific axon regeneration in the zebrafish vagus nerve.

Isabella, Adam J / Stonick, Jason A / Dubrulle, Julien / Moens, Cecilia B

Development (Cambridge, England)

2021 Volume 148, Issue 18

Abstract: Regeneration after peripheral nerve damage requires that axons re-grow to the correct target tissues in a process called target-specific regeneration. Although much is known about the mechanisms that promote axon re-growth, re-growing axons often fail to ...

Abstract	Regeneration after peripheral nerve damage requires that axons re-grow to the correct target tissues in a process called target-specific regeneration. Although much is known about the mechanisms that promote axon re-growth, re-growing axons often fail to reach the correct targets, resulting in impaired nerve function. We know very little about how axons achieve target-specific regeneration, particularly in branched nerves that require distinct targeting decisions at branch points. The zebrafish vagus motor nerve is a branched nerve with a well-defined topographic organization. Here, we track regeneration of individual vagus axons after whole-nerve laser severing and find a robust capacity for target-specific, functional re-growth. We then develop a new single-cell chimera injury model for precise manipulation of axon-environment interactions and find that (1) the guidance mechanism used during regeneration is distinct from the nerve's developmental guidance mechanism, (2) target selection is specified by neurons' intrinsic memory of their position within the brain, and (3) targeting to a branch requires its pre-existing innervation. This work establishes the zebrafish vagus nerve as a tractable regeneration model and reveals the mechanistic basis of target-specific regeneration.
MeSH term(s)	Animals ; Animals, Genetically Modified/physiology ; Axons/physiology ; Gene Expression Regulation, Developmental/physiology ; Nerve Regeneration/physiology ; Neurons/physiology ; Peripheral Nerve Injuries/physiopathology ; Vagus Nerve/physiology ; Zebrafish/physiology
Language	English
Publishing date	2021-09-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.199706
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Article ; Online: Bystander interaction with a novel multipurpose medical drone: A simulation trial.

Leith, Thomas / Correll, Jason A / Davidson, Emma E / Gottula, Adam L / Majhail, Noor K / Mathias, Emily J / Pribble, James / Roberts, Nathan B / Scott, Isabella G / Cranford, James A / Hopson, Laura R / Hunt, Nathaniel / Brent, Christine M

Resuscitation plus

2024 Volume 18, Page(s) 100633

Abstract: Intro: Medical drones are an emerging technology which may facilitate rapid treatment in time-sensitive emergencies. However, drones rely on lay rescuers, whose interactions with multipurpose medical drones have not been studied, and the optimal drone ... ...

Abstract	Intro: Medical drones are an emerging technology which may facilitate rapid treatment in time-sensitive emergencies. However, drones rely on lay rescuers, whose interactions with multipurpose medical drones have not been studied, and the optimal drone design remains unclear. Methods: We conducted 24 simulations of adult out-of-hospital cardiac arrest (OHCA) and pediatric anaphylaxis with a prototype drone equipped with spoken and visual cues and a multipurpose medical kit. 24 layperson volunteers encountered one of the two scenarios and were supported through administering treatment by a simulated 911 dispatcher. Bystander-drone interactions were evaluated via a convergent parallel mixed methods approach using surveys, video event review, and semi-structured interviews. Results: 83% (20/24) of participants voiced comfort interacting with the drone. 96% (23/24) were interested in future interaction. Participants appreciated the drone's spoken instructions but found visual cues confusing. Participants retrieved the medical kit from the drone in a mean of 5 seconds (range 2-14) of drone contact; 79% (19/24) found this step easy or very easy. The medical kit's layered design caused difficulty in retrieving appropriate equipment. Participants expressed a wide range of reactions to the unique drone design. Conclusions: Laypeople can effectively and comfortably interact with a medical drone with a novel design. Feedback on design elements will result in further refinements and valuable insights for other drone designers. A multipurpose medical kit created more challenges and indicates the need for further refinement to facilitate use of the equipment.
Language	English
Publishing date	2024-04-16
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-5204
ISSN (online)	2666-5204
DOI	10.1016/j.resplu.2024.100633
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Article ; Online: Outcomes After Pharyngeal Flap Surgery in Children: A Comparison of Lined Versus Unlined Flaps.

Fuller, Colin / Reed Gardner, J / Speed, Olivia / Thomason, Ashlen / Zaniletti, Isabella / Buckmiller, Lisa / Johnson, Adam / Hartzell, Larry

The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association

2023 , Page(s) 10556656231172642

Abstract: Objective: The addition of a uvular flap (PFU) was hypothesized to improve outcomes over standard pharyngeal flap (PF) for correction of velopharyngeal dysfunction. We report differences in outcomes of PF vs PFU at our institution.: Design: ... ...

Abstract	Objective: The addition of a uvular flap (PFU) was hypothesized to improve outcomes over standard pharyngeal flap (PF) for correction of velopharyngeal dysfunction. We report differences in outcomes of PF vs PFU at our institution. Design: Retrospective cohort study. Setting: Tertiary children's hospital. Patients: Children who underwent PF or PFU with the three highest-volume surgeons at our institution in 2004-2017. Outcome measures: We examined differences in complications between groups, frequency and type of revision surgery, and speech-related measures including nasometry, pressure-flow testing (PFT) and perceptual speech analysis (PSA). Results: 160 patients were included, 41 PF and 119 PFU (including 18 with Hogan technique). Patients undergoing PFU were older (7.6 yr vs 6.0 yr; p = 0.037) and more likely to have cleft palate (63/119 vs 14/41; p = 0.047). There was no significant difference in complications. With PFU, a decrease in airspace contracting revision surgeries was noted, (4/119 vs 8/41; p = 0.002) which drove a reduction in revision surgery of all types (7/119 vs 13/41; p = 0.033). However, patients that did undergo revision surgery after PFU underwent more revision procedures (p = 0.032). PSA scores were found to be lower (less hypernasal) after PFU (p = 0.009) compared to PF. Objective speech measures had varying results, with nasometry demonstrating a significant difference between groups (p = 0.001), while PFT (p = 0.525) did not demonstrate a statistical difference. Conclusion: The use of a uvular lining flap in pharyngeal flap surgery may be associated with improved long term surgical outcomes, including both improvements in subjective and objective testing and a lower rate of revision surgery, without increased complications.
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1069409-2
ISSN	1545-1569 ; 0009-8701 ; 1055-6656
ISSN (online)	1545-1569
ISSN	0009-8701 ; 1055-6656
DOI	10.1177/10556656231172642
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Article: Dietary nitrate ingested with and without pomegranate supplementation does not improve resistance exercise performance.

Tan, Rachel / Price, Katherine M / Wideen, Lauren E / Lincoln, Isabella G / Karl, Sean T / Seals, Jacob P / Paniagua, Keonabelle K / Hagen, Dylan W / Tchaprazian, Isaac / Bailey, Stephen J / Pennell, Adam

Frontiers in nutrition

2023 Volume 10, Page(s) 1217192

Abstract: This study tested the hypothesis that co-ingesting nitrate ( ... ...

Abstract	This study tested the hypothesis that co-ingesting nitrate (NO
Language	English
Publishing date	2023-07-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2023.1217192
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Article ; Online: Retinoic Acid Organizes the Zebrafish Vagus Motor Topographic Map via Spatiotemporal Coordination of Hgf/Met Signaling.

Isabella, Adam J / Barsh, Gabrielle R / Stonick, Jason A / Dubrulle, Julien / Moens, Cecilia B

Developmental cell

2020 Volume 53, Issue 3, Page(s) 344–357.e5

Abstract: Information flow through neural circuits often requires their organization into topographic maps in which the positions of cell bodies and synaptic targets correspond. To understand how topographic map development is controlled, we examine the mechanism ... ...

Abstract	Information flow through neural circuits often requires their organization into topographic maps in which the positions of cell bodies and synaptic targets correspond. To understand how topographic map development is controlled, we examine the mechanism underlying targeting of vagus motor axons to the pharyngeal arches in zebrafish. We reveal that retinoic acid organizes topography by specifying anterior-posterior identity in vagus motor neurons. We then show that chemoattractant signaling between Hgf and Met is required for vagus innervation of the pharyngeal arches. Finally, we find that retinoic acid controls the spatiotemporal dynamics of Hgf/Met signaling to coordinate axon targeting with the developmental progression of the pharyngeal arches and show that experimentally altering the timing of Hgf/Met signaling is sufficient to redirect axon targeting and disrupt the topographic map. These findings establish a mechanism of topographic map development in which the regulation of chemoattractant signaling in space and time guides axon targeting.
MeSH term(s)	Animals ; Branchial Region/drug effects ; Branchial Region/physiology ; Gene Expression Regulation, Developmental/drug effects ; Hepatocyte Growth Factor/genetics ; Hepatocyte Growth Factor/metabolism ; Keratolytic Agents/pharmacology ; Proto-Oncogene Proteins c-met/genetics ; Proto-Oncogene Proteins c-met/metabolism ; Signal Transduction ; Spatio-Temporal Analysis ; Tretinoin/pharmacology ; Vagus Nerve/drug effects ; Vagus Nerve/physiology ; Zebrafish/physiology ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
Chemical Substances	Keratolytic Agents ; Zebrafish Proteins ; Tretinoin (5688UTC01R) ; Hepatocyte Growth Factor (67256-21-7) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Language	English
Publishing date	2020-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2020.03.017
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Article ; Online: Met is required for oligodendrocyte progenitor cell migration in Danio rerio.

Ali, Maria F / Latimer, Andrew J / Wang, Yinxue / Hogenmiller, Leah / Fontenas, Laura / Isabella, Adam J / Moens, Cecilia B / Yu, Guoqiang / Kucenas, Sarah

G3 (Bethesda, Md.)

2021 Volume 11, Issue 10

Abstract: During vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping ... ...

Abstract	During vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping domains. While this process of developmental OPC migration is well characterized, the nature of the molecular mediators that govern it remain largely unknown. Here, using zebrafish as a model, we demonstrate that Met signaling is required for initial developmental migration of OPCs, and, using cell-specific knock-down of Met signaling, show that Met acts cell-autonomously in OPCs. Taken together, these findings demonstrate in vivo, the role of Met signaling in OPC migration and provide new insight into how OPC migration is regulated during development.
MeSH term(s)	Animals ; Cell Differentiation ; Oligodendrocyte Precursor Cells ; Oligodendroglia ; Signal Transduction ; Spinal Cord ; Zebrafish
Language	English
Publishing date	2021-09-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkab265
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