Functional Regeneration in the Larval Zebrafish Spinal Cord

Bhatt, Dimple H.; Patzelova, Hana; McLean, Dianne L.; Fetcho, Joseph R.; Zottoli, Steven J.

doi:10.1002/9783527610365.ch9

Cited by 3 publications

(9 citation statements)

References 112 publications

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“…The Mauthner cells seldom regrow their axons past the level of spinal cord transections in the larval lamprey (Jacobs et al, ; Shifman et al, ) and zebrafish (Bhatt, Otto, Depoister, & Fetcho, ). Rather, sprouts follow aberrant pathways which are not conducive for the return of function (lamprey: Yin & Selzer, ; Jacobs et al, ; Lurie, Pijak, & Selzer, ; zebrafish: Becker, Wullimann, Becker, Bernhardt, & Schachner, ; Becker et al, ; goldfish: Titmus, Faber, & Zottoli, ; Zottoli et al, ; reviewed in Bhatt, Patzelova, McLean, Fetcho, & Zottoli, ). For example, sprouting of larval zebrafish M‐axons occurred in 15 of 43 animals but only one crossed the lesion (Bhatt et al, ).…”

Section: Discussionmentioning

confidence: 99%

Invasion of microglia/macrophages and granulocytes into the Mauthner axon myelin sheath following spinal cord injury of the adult goldfish, Carassius auratus

Koganti

DeMajewski

et al. 2019

Journal of Morphology

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Rapid activation of resident glia occurs after spinal cord injury. Somewhat later, innate and adaptive immune responses occur with the invasion of peripheral immune cells into the wound site. The activation of resident and peripheral immune cells has been postulated to play harmful as well as beneficial roles in the regenerative process. Mauthner cells, large identifiable neurons located in the hindbrain of most fish and amphibians, provided the opportunity to study the morphological relationship between reactive cells and Mauthner axons (M‐axons) severed by spinal cord crush or by selective axotomy. After crossing in the hindbrain, the M‐axons of adult goldfish, Carassius auratus, extend the length of the spinal cord. Following injury, the M‐axon undergoes retrograde degeneration within its myelin sheath creating an axon‐free zone (proximal dieback zone). Reactive cells invade the wound site, enter the axon‐free dieback zone and are observed in the vicinity of the retracted M‐axon tip as early as 3 hr postinjury. Transmission electron microscopy allowed the detection of microglia/macrophages and granulocytes, some of which appear to be neutrophil‐like, at each of these locations. We believe that this is the first report of the invasion of such cells within the myelin sheath of an identifiable axon in the vertebrate central nervous system (CNS). We speculate that microglia/macrophages and granulocytes that are attracted within a few hours to the damaged M‐axon are part of an inflammatory response that allows phagocytosis of debris and plays a role in the regenerative process. Our results provide the baseline from which to utilize immunohistochemical and genetic approaches to elucidate the role of non‐neuronal cells in the regenerative process of a single axon in the vertebrate CNS.

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Section: Discussionmentioning

confidence: 99%

Invasion of microglia/macrophages and granulocytes into the Mauthner axon myelin sheath following spinal cord injury of the adult goldfish, Carassius auratus

Koganti

DeMajewski

et al. 2019

Journal of Morphology

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“…While axonal regrowth and behavioral recovery after spinal cord injury is best studied in the larval and adult lamprey, there are several other vertebrate species known to be capable of regenerating various CNS components (Bhatt et al , 2007; Tanaka and Ferretti, 2009). In teleost fishes, as in lampreys, some RS neurons have the capacity to regenerate and recover functionality, while others do not.…”

Section: Toward a Comparative Gene Regulatory Network Approach: Centrmentioning

confidence: 99%

“…RS neurons in larval zebrafish are optically accessible, allowing studies on the role of Mauthner neurons and other RS neurons in startle behavior (O’Malley et al , 1996; Fetcho et al , 1998; Liu and Fetcho, 1999; Gahtan et al , 2002; Nakayama and Oda, 2004). In addition, the functional consequences of neuronal regrowth can be assayed in a living zebrafish (Bhatt et al , 2007). CNS regeneration also occurs in the adult zebrafish (Becker et al , 1997; Becker and Becker, 2008), ultimately allowing a direct comparison with CNS regeneration in the larval zebrafish.…”

Section: Toward a Comparative Gene Regulatory Network Approach: Centrmentioning

confidence: 99%

“…CNS regeneration also occurs in the adult zebrafish (Becker et al , 1997; Becker and Becker, 2008), ultimately allowing a direct comparison with CNS regeneration in the larval zebrafish. As in lamprey, regenerative capacity can also be modulated in the larval zebrafish: Mauthner axons demonstrate minimal regeneration after spinal cord damage (Bhatt et al , 2004), but when cAMP is electroporated into the soma, axons sprout and functional regeneration occurs (Bhatt et al , 2004, 2007). Indeed, the ability to enhance regeneration or “convert” a non-regenerating neuron to a regenerating one by increasing intracellular cAMP has been observed in many species (Bhatt et al , 2004; Hannila and Filbin, 2008; Jin et al , 2009; Ghosh-Roy et al ., 2010), and challenges the hypothesis that certain central neurons have an intrinsic inability to regenerate (Kiernan, 1979).…”

Section: Toward a Comparative Gene Regulatory Network Approach: Centrmentioning

confidence: 99%

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Regeneration in the Era of Functional Genomics and Gene Network Analysis

Smith

Morgan

Zottoli

et al. 2011

The Biological Bulletin

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What gives an organism the ability to regrow tissues and to recover function where another organism fails is the central problem of regenerative biology. The challenge is to describe the mechanisms of regeneration at the molecular level, delivering detailed insights into the many components that are cross-regulated. In other words, a broad, yet deep dissection of the system-wide network of molecular interactions is needed. Functional genomics has been used to elucidate gene regulatory networks (GRNs) in developing tissues, which, like regeneration, are complex systems. Therefore, we reason that the GRN approach, aided by next generation technologies, can also be applied to study the molecular mechanisms underlying the complex functions of regeneration. We ask what characteristics a model system must have to support a GRN analysis. Our discussion focuses on regeneration in the central nervous system, where loss of function has particularly devastating consequences for an organism. We examine a cohort of cells conserved across all vertebrates, the reticulospinal (RS) neurons, which lend themselves well to experimental manipulations. In the lamprey, a jawless vertebrate, there are giant RS neurons whose large size and ability to regenerate make them particularly suited for a GRN analysis. Adding to their value, a distinct subset of lamprey RS neurons reproducibly fail to regenerate, presenting an opportunity for side-by-side comparison of gene networks that promote or inhibit regeneration. Thus, determining the GRN for regeneration in RS neurons will provide a mechanistic understanding of the fundamental cues that lead to success or failure to regenerate.

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“…The time course to regain substantial behavioral recovery in adult zebrafish is approximately 1 month for either a crush or transection injury (Becker et al, 2004; Becker et al, 1997; Hui et al, 2010). After spinal cord transection and treatment with cAMP in larval zebrafish, recovery of escape responses can be observed 3-5 days after injury (Becker et al, 2004; Becker et al, 1997; Bhatt et al, 2004; Bhatt et al, 2007). For an illustration of zebrafish axons regenerating across the lesion site, see Figure 2B.…”

Section: Introductionmentioning

confidence: 99%

Non-mammalian model systems for studying neuro-immune interactions after spinal cord injury

Bloom¹

2014

Experimental Neurology

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Mammals exhibit poor recovery after injury to the spinal cord, where the loss of neurons and neuronal connections can be functionally devastating. In contrast, it has long been appreciated that many non-mammalian vertebrate species exhibit significant spontaneous functional recovery after spinal cord injury (SCI). Identifying the biological responses that support an organism's inability or ability to recover function after SCI is an important scientific and medical question. While recent advances have been made in understanding the responses to SCI in mammals, we remain without an effective clinical therapy for SCI. A comparative biological approach to understanding responses to SCI in non-mammalian vertebrates will yield important insights into mechanisms that promote recovery after SCI. Presently, mechanistic studies aimed at elucidating responses, both intrinsic and extrinsic to neurons, that result in different regenerative capacities after SCI across vertebrates are just in their early stages. There are several inhibitory mechanisms proposed to impede recovery from SCI in mammals, including reactive gliosis and scarring, myelin associated proteins, and a suboptimal immune response. One hypothesis to explain the robust regenerative capacity of several non-mammalian vertebrates is a lack of some or all of these inhibitory signals. This review presents the current knowledge of immune responses to SCI in several non-mammalian species that achieve anatomical and functional recovery after SCI. This subject is of growing interest, as studies increasingly show both beneficial and detrimental roles of the immune response following SCI in mammals. A long-term goal of biomedical research in all experimental models of SCI is to understand how to promote functional recovery after SCI in humans. Therefore, understanding immune responses to SCI in non-mammalian vertebrates that achieve functional recovery spontaneously may identify novel strategies to modulate immune responses in less regenerative species and promote recovery after SCI.

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Functional Regeneration in the Larval Zebrafish Spinal Cord

Cited by 3 publications

References 112 publications

Invasion of microglia/macrophages and granulocytes into the Mauthner axon myelin sheath following spinal cord injury of the adult goldfish, Carassius auratus

Invasion of microglia/macrophages and granulocytes into the Mauthner axon myelin sheath following spinal cord injury of the adult goldfish, Carassius auratus

Regeneration in the Era of Functional Genomics and Gene Network Analysis

Non-mammalian model systems for studying neuro-immune interactions after spinal cord injury

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