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PubMed1996

Neurofilament spacing, phosphorylation, and axon diameter in regenerating and uninjured lamprey axons.

It has been postulated that phosphorylation of the carboxy terminus sidearms of neurofilaments (NFs) increases axon diameter through repulsive electrostatic forces that increase sidearm extension and interfilament spacing. To evaluate this hypothesis, the relationships among NF phosphorylation, NF spacing, and axon diameter were examined in uninjured and spinal cord-transected larval sea lampreys (Petromyzon marinus). In untransected animals, axon diameters in the spinal cord varied from 0.5 to 50 microns. Antibodies specific for highly phosphorylated NFs labeled only large axons (> 10 microns), whereas antibodies for lightly phosphorylated NFs labeled medium-sized and small axons more darkly than large axons. For most axons in untransected animals, diameter was inversely related to NF packing density, but the interfilament distances of the largest axons were only 1.5 times those of the smallest axons. In addition, the lightly phosphorylated NFs of the small axons in the dorsal columns were widely spaced, suggesting that phosphorylation of NFs does not rigidly determine their spacing and that NF spacing does not rigidly determine axon diameter. Regenerating neurites of giant reticulospinal axons (GRAs) have diameters only 5-10% of those of their parent axons. If axon caliber is controlled by NF phosphorylation via mutual electrostatic repulsion, then NFs in the slender regenerating neurites should be lightly phosphorylated and densely packed (similar to NFs in uninjured small caliber axons), whereas NFs in the parent GRAs should be highly phosphorylated and loosely packed. However, although linear density of NFs (the number of NFs per micrometer) in these slender regenerating neurites was twice that in their parent axons, they were highly phosphorylated. Following sectioning of these same axons close to the cell body, axon-like neurites regenerated ectopically from dendritic tips. These ectopically regenerating neurites had NF linear densities 2.5 times those of uncut GRAs but were also highly phosphorylated. Thus, in the lamprey, NF phosphorylation may not control axon diameter directly through electrorepulsive charges that increase NF sidearm extension and NF spacing. It is possible that phosphorylation of NFs normally influences axon diameter through indirect mechanisms, such as the slowing of NF transport and the formation of a stationary cytoskeletal lattice, as has been proposed by others. Such a mechanism could be overridden during regeneration, when a more compact, phosphorylated NF backbone might add mechanical stiffness that promotes the advance of the neurite tip within a restricted central nervous system environment.

Animals↗
PubMed1996

Intrinsic versus extrinsic factors in determining the regeneration of the central processes of rat dorsal root ganglion neurons: the influence of a peripheral nerve graft.

The relative contribution of intrinsic growth capacity versus extrinsic growth-promoting factors in determining the capacity of transected dorsal root axons to regenerate long distances was studied. L4 dorsal root axons regenerating into 4-cm peripheral nerve grafts on transected dorsal roots were counted. Few dorsal root myelinated axons regenerated to the distal end of the grafts by 10 weeks unless the sciatic nerve was also crushed. Regeneration of unmyelinated axons was also increased by peripheral lesions. Crush or transection of the dorsal roots without grafting did not alter GAP-43 mRNA expression in L4 dorsal root ganglion (DRG) cells. Grafting a peripheral nerve onto the cut end of an L4 dorsal root doubled the number of DRG cells expressing high levels of GAP-43 mRNA after a delay of several weeks. Peripheral nerve crush at the time of nerve grafting resulted in a very rapid rise in GAP-43 mRNA expression, which then declined to a steady level, twice that of controls, by 7 weeks. Thus, the rapid increase in the number of DRG neurons expressing high levels of GAP-43 mRNA after peripheral but not central axotomy correlates with the regeneration of central axons through nerve grafts. Because GAP-43 mRNA is slowly upregulated in a subpopulation of sensory neurons in response to exposure of their central axons to a peripheral nerve environment, environments favourable for axonal growth may act by increasing the intrinsic growth response of neurons. Lack of intrinsic growth capacity may contribute to the failure of dorsal root axons to regenerate into the spinal cord.

Animals↗
PubMed1996

Attempts to facilitate dorsal column axonal regeneration in a neonatal spinal environment.

The response to injury of ascending collaterals of dorsal root axons within the dorsal column (DC) was studied after neonatal spinal overhemisection (OH) made at different levels of the spinal cord. The transganglionic tracer, cholera toxin conjugated to horseradish peroxidase, and the anterograde tracer, biotinylated dextran amine, were used to label dorsal root ganglion cells with peripheral axons contributing to the sciatic nerve. There was no indication of a regenerative attempt by DC axons at acute survival times (3 days and later) after cervical injury, replicating previous work done at chronic survival periods (Lahr and Stelzner [1990] J. Comp. Neurol. 293:377-398). There was also no evidence of DC regeneration after lumbar OH injury even though immunohistochemical studies using the oligodendrocyte markers Rip and myelin basic protein showed few oligodendrocytes in the gracile fasciculus at lumbar levels at birth. Therefore, the lack of myelin in the dorsal funiculus at lumbar levels does not enhance the growth of neonatally axotomized DC axons. In addition, DC axons did not regenerate when presented with fetal spinal tissue implanted into thoracic OH lesions, even though positive control experiments showed that segmental dorsal root axons containing calcition gene-related peptide and corticospinal axons grew into these implants, replicating previous work of others. When a thoracic OH lesion, with or without a fetal spinal implant, was combined with sciatic nerve injury to attempt to stimulate an intracellular regenerative response of DRG neurons, again, no evidence of DC axonal regeneration was detected. Quantitative studies of the L4 and L5 dorsal root ganglia (DRG) showed that OH injury did not result in DRG neuronal loss. However, sciatic nerve injury did result in significant post-axotomy retrograde cell loss of DRG neurons, even in groups receiving thoracic embryonic spinal implants, and is one explanation for the minimal effect of sciatic nerve injury on DC regeneration. Although fetal tissue did not appear to rescue a significant number of DRG neurons, the quantitative analysis showed an enlargement of the largest class of DRG neuron, the class that contributes to the DC projection, in all groups receiving fetal tissue implants. This apparent trophic effect did not affect DC regeneration or neuronal survival after peripheral axotomy. Further studies are needed to determine why DC axons do not regenerate in a neonatal spinal environment or within fetal tissue implants, especially because previous work by others in both the developing and adult spinal cord shows that dorsal root axons will grow within the same type of fetal spinal implant.

Animals↗
PubMed1999

Axonal regeneration in the central nervous system of aplysia californica determined by anterograde transport of biocytin.

Rhythmic biting, a component of consummatory feeding behavior in the sea hare Aplysia californica, is eliminated following bilateral cerebral-buccal connective (CBC) crushes and recovers within 14 days postlesion. To assess axonal regeneration after CBC lesions, we used biocytin backfills of CBCs followed by fluorescence labeling with streptavidin-lissamine rhodamine. Anterograde transport of biocytin showed up to 1 mm of outgrowth by regenerating axons at 3 days postlesion. At 7 days postlesion, the regenerated axons approached or had entered the ipsilateral buccal neuropil and exhibited numerous varicosities; the average rate of axonal growth was 326 microm/day for the longest, most rapidly growing axons labeled in the CBC. The number of varicosities on labeled axons, suggestive of intercellular interactions, was increased dramatically at all times postlesion. At 14 and 20 days postlesion, regenerated axons branched extensively in the ipsilateral buccal neuropil, entered the contralateral buccal neuropil, and entered peripheral nerves on both sides of the midline. At these later times postlesion, some labeled axons encircled unlabeled buccal cell bodies and exhibited branches containing numerous varicosities, indicative of axosomatic contacts. Some regenerating axons were observed in the sheath of the CBC, but the vast majority of labeled axons remained confined to the connective core, as in control preparations. The bilateral projections within the buccal ganglia of labeled cerebral-to-buccal axons and the large number of varicosities present on these processes are indicative of regenerating axons and synapses that likely contribute to the functional recovery of rhythmic biting.

Animals↗
PubMed2000

Temporal, spatial, and morphologic features of hair cell regeneration in the avian basilar papilla.

Hair cell-selective antibodies were used in combination with the nucleotide bromode-oxyuridine (BrdU) to examine the temporal, spatial, and morphologic progression of auditory hair cell regeneration in chicks after a single gentamicin injection. New hair cells are first identifiable with an antibody to class III beta (beta) tubulin (TuJ1) by 14 hours after BrdU incorporation, but progenitor cells in S phase and M phase are TuJ1-negative. TuJ1 labeling reveals that new hair cells are first detected at 3 days after gentamicin, in the base, and the emergence and maturation of regenerating hair cells spreads apically over time. Differentiation of regenerating hair cells consists of a progressive series of morphologic changes. During early differentiation (14 hours to 1 day after BrdU), regenerating hair cells are round or fusiform and remain near the lumen, where they are generated. During intermediate differentiation (2-4 days after BrdU), regenerating hair cells resemble support cells; their somata are elongated, their nuclei are in the support cell layer, and they appear to contact both the lumenal surface and the basal lamina. The 275-kDa hair cell antigen is first expressed in regenerating hair cells during this period. During late differentiation (7 days after BrdU and later), TuJ1-positive cells acquire the globose shape of mature hair cells. Labeling with antibodies to hair cell antigen, calmodulin, and ribosomal RNA confirms this morphologic progression. Examination of sister cells born at 3 days post-gentamicin reveals that there is equal likelihood that they will assume the hair cell or support cell fate (i.e., both asymmetric and symmetric differentiation occur).

Animals↗
PubMed2000

Connective tissue response to tubular implants for peripheral nerve regeneration: the role of myofibroblasts.

The presence of contractile cells, their organization around regenerating nerve trunks, and the hypothetical effect of these organized structures on the extent of regeneration across a tubulated 10-mm gap in the rat sciatic nerve were investigated. Collagen and silicone tubes were implanted both empty and filled with a collagen-glycosaminoglycan (GAG) matrix. Nerves were retrieved at 6, 30, and 60 weeks postoperatively and time-dependent values of the nerve trunk diameter along the tubulated length were recorded. The presence of myofibroblasts was identified immunohistochemically using a monoclonal antibody to alpha-smooth muscle actin. Myofibroblasts were circumferentially arranged around the perimeter of regenerated nerve trunks, forming a capsule which was about 10 times thicker in silicone tubes than in collagen tubes. The nerve trunk diameter that formed inside collagen tubes was twice as large as that inside silicone tubes. In contrast, the collagen-GAG matrix had a relatively small effect on capsule thickness or diameter of regenerate. It was hypothesized that the frequency of successful bridging by axons depends on the balance between two competitive forces: the axial forces generated by the outgrowth of axons and nonneuronal cells from the proximal stump and the constrictive, circumferential forces imposed by the contractile tissue capsule that promote closure of the wounded stumps and prevent axon elongation. Because the presence of the collagen-GAG matrix has enhanced greatly the recovery of normal function of regenerates in silicone tubes, it was hypothesized that it accelerated axonal elongation sufficiently before the hypothetical forces constricting the nerve trunk in silicone tubes became sufficiently large. The combined data suggest a new mechanism for peripheral nerve regeneration along a tubulated gap.

Actins↗
PubMed1998

Cellular mechanisms of intestine regeneration in the sea cucumber, Holothuria glaberrima Selenka (Holothuroidea:Echinodermata).

Echinoderms are the deuterostome group with the most striking capacity to regenerate lost body parts. In particular, members of the class Holothuroidea are able to regenerate most of their internal organs following a typical evisceration process. Such formation of new viscera in an adult organism provides a unique model to study the process of organogenesis. We have studied this process in the sea cucumber Holothuria glabberrima by describing the spatial and temporal pattern of cellular events that occur during intestine regeneration following chemically induced evisceration. Regeneration begins as a thickening of the mesenteries that supported the autotomized organs to the body wall. The mesenterial thickening consists of tissues where most of the cellular populations found in the normal intestine are already present. However, the cell numbers differ, particularly those of hemocytes and amoebocytes, suggesting that some of these cells play an important role in the formation of the solid rod of hypertrophic mesentery that characterizes the intestinal primordia. The appearance of the luminal epithelium, together with the formation of the lumen, occurs during the second week of regeneration by proliferation and extensive migration of cells from the esophagus and cloacal ends into the thickenings. At this stage all tissue layers are present, but it takes an additional week for them to exhibit the proportions typical of the normal organ. Cell division, as determined by BrdU labeling, mainly occurs in the coelomic epithelia of the hypertrophic mesentery and in the regenerating luminal epithelium. Our study provides evidence that the process of new organ formation in holothurians can be described as an intermediate process showing characteristics of both epimorphic and morphallactic phenomena.

Animals↗
PubMed1996

Clonal cell cultures from adult spinal cord of the amphibian urodele Pleurodeles waltl to study the identity and potentialities of cells during tail regeneration.

The urodele amphibians are nearly the only adult vertebrates able to regenerate their missing or amputated tail. The most striking feature of this model lies in the ability of the spinal cord (SC) to differentiate, within the regenerating tail, a new ependymal tube from which the SC and the peripheral nervous system originate. A fundamental question is whether, in response to tail excision, the ependymoglia of the old SC stump behaves as an embryonic neuroepithelium. To evaluate this possibility, cell lines from primary cell cultures of adult SC were established for the first time in newts, and two cell clones, immunochemically characterized as ependymoglial cell populations, could be obtained. To analyze the potentialities of these clonal cells, after transplantation in tail regenerates, cell-marking experiments, using either in vitro transfection with lacZ gene or the lineage tracer lysinated rhodamine dextran (LRD), were performed. One to 2 weeks postimplantation, most of labeled derivatives were identified as melanocytes. Interestingly, labeled cells were also seen integrated in the ependymoglia of the regenerating SC. Two to 6 weeks after implantation in young regenerates, we also observed LRD-labeled elongated cells close to nerves or myofibers which were unambiguously identified as Schwann cells by galactocerebroside staining. Taken together, these findings showed that clonal cells derived from adult newt SC cultures could largely find, in regenerate mesenchyme, suitable environmental conditions to differentiate into melanocytes or Schwann cells. Because these two cells types arise from neural crest cells during embryo-genesis, this supports the interesting view that multipotent cells are still present in the SC of adult urodeles.

Animals↗
PubMed2000

Neural and hormonal control of expression of myogenic regulatory factor genes during regeneration of Xenopus fast muscles: myogenin and MRF4 mRNA accumulation are neurally regulated oppositely.

With the aim to investigate the influence of both innervation and thyroid hormone, on the expression of the MRFs during muscle regeneration, we performed cardiotoxin injury-induced regeneration experiments on fast muscles of adult Xenopus laevis subjected to different experimental conditions, including denervation and T3 treatment, and analyzed the accumulation of the four myogenic regulatory factors (MRFs) using RT-PCR and in situ hybridization. We show here that manipulation of hormone levels or innervation resulted in differential alterations of MRF expression. Denervation and T3 treatment transiently down-regulated Myf-5 mRNA levels at the beginning of the regeneration process. Myf-5 was the only myogenic factor subject to thyroid hormone influence. Muscle denervation persistently reduces the levels of MRF4 transcripts as early as the first stages of regeneration, whereas the levels of myogenin mRNA were increased in the late stages of regeneration. This suggests that MRF4 expression may be induced by innervation and hence may be involved in mediating transcriptional responses to innervation and that myogenin expression may compensate for the down-regulation of MRF4 gene. This switch in MRF gene expression following denervation could have important consequences for the ability of Xenopus regenerating muscles to recover function after denervation.

Animals↗
PubMed1996

Immunohistochemical localization of cell adhesion molecules and cell-cell contact proteins during regeneration of the rat optic nerve induced by sciatic nerve autotransplantation.

BACKGROUND: The central nervous system neurons of adult mammals are known to regenerate into peripheral nerve autograft. The localization of cell adhesion molecules and cell-cell contact proteins were studied during axonal regeneration induced by sciatic nerve autotransplantation. METHODS: A sciatic nerve autograft was anastomosed to the proximal stump of the transected rat optic nerve. Immunofluorescence microscopy, thin sectioning, and immunoelectron microscopy with the preembedding method and ultrathin cryosections were used to localize cell adhesion molecules (L1; neural cell adhesion molecule, NCAM; myelin-associated glycoprotein, MAG) and cell-cell contact proteins (connexins 32, 43, ZO-1) at 3 days to 4 weeks postoperation. RESULTS: Most regenerating axons contacted astrocytes in the optic nerve and Schwann cells in the graft. Immunoreactivity of NCAM was widely distributed along the surface of axons, astrocytes, Schwann cells, and perineurial cells. The L1 immunoreactivity was confined to the interface of axon-astrocyte and of axon-Schwann cell. MAG immunoreactivity was seen at the interface of axon and myelin within the graft. Connexins 32, 43, and ZO-1 immunoreactivities were observed at contact sites between axons and Schwann cells within the graft. CONCLUSIONS: Cell adhesion molecules (L1, NCAM, MAG) are localized at the cell surface of regenerating axons, astrocytes, and Schwann cells during optic nerve regeneration elicited by peripheral nerve graft. Cell-cell contact proteins (connexins 32, 43, ZO-1) are present at the interface between axons and Schwann cells in the graft. Our results suggest that these molecules are involved in cell adhesion events during optic nerve regeneration.

Animals↗
PubMed1997

Cholesterol reutilization during myelination of regenerating PNS axons is impaired in Niemann-Pick disease type C mice.

Niemann-Pick C (NPC) disease is an autosomal recessive lipidosis characterized by lysosomal accumulations of unesterified cholesterol. Cultured NPC cells exhibit a defect in the intracellular trafficking of LDL-derived cholesterol that leads to lysosomal accumulations of unesterified cholesterol. We found in a preliminary study that the myelination of regenerating axons was retarded in the NPC mouse following sciatic nerve crush. Because lipoprotein-mediated cholesterol transport is involved in myelination during nerve regeneration, we investigated whether this cholesterol reutilization pathway was perturbed in the NPC mouse. Mice received intraneural injections of [3H]acetate to label myelin cholesterol, and 2 weeks later the injected nerves were crushed above the injection site. Four weeks after crush, the nerves were examined by electron microscopic autoradiography. In normal mice, regeneration was well advanced, with thick myelin sheaths surrounding the regenerated axons and very little myelin debris remaining. The new myelin sheaths were well labeled, indicative of efficient cholesterol reutilization. In NPC mice, the new myelin sheaths were thinner and contained little label, indicative of retarded regeneration and little or no cholesterol reutilization. These data suggest the possibility of a causal link between compromised cholesterol reutilization and delayed or slowed regeneration of myelin sheaths.

Animals↗
PubMed1997

The role of leukemia inhibitory factor in skeletal muscle regeneration.

Although a number of cytokines have been implicated in tissue regeneration, it is unknown which ones actually function in vivo. Here, we use mice with a targeted mutation in the leukemia inhibitory factor (LIF) gene to examine the role of LIF in muscle regeneration. Using a muscle crush model, we show that muscle regeneration in LIF knockout mice is significantly, reduced compared to control littermates. Further, targeted infusion of LIF in both normal and LIF knockout animals stimulated muscle regeneration, but the stimulation observed was much greater in the mutant animals than in controls. In contrast, interleukin-6 and transforming growth factor-alpha, which also stimulate myoblast proliferation in vitro, had no effect on regeneration. These findings demonstrate directly that LIF is involved in regeneration of injured muscle and points to the use of LIF as a therapeutic agent in the treatment of neuromuscular disease.

Animals↗
PubMed1999

Use of small intestinal submucosal implants for regeneration of large fascial defects: an experimental study in dogs.

A single layer of porcine small intestinal submucosa (SIS) was sutured into a 5 x 5 cm window created in the fascia lata of ten adult mongrel dogs in order to determine the efficacy of this material in promoting tissue regeneration of large fascial defects. A similar defect in the contralateral limb was left empty and served as a negative control. Tissue regeneration was examined grossly and histologically at 6 and 12 weeks. By 6 weeks, marked fibroplasia and angiogenesis had occurred throughout the SIS scaffold. The regenerated tissue was well organized and showed good integration with the adjacent fascia while the control specimens were filled with loose areolar connective tissue. At 12 weeks the experimental defects were filled with a regenerated tissue that grossly and histologically resembled normal fascia. There was no evidence of adhesions to the underlying musculature. Conversely, the tissue that filled the control defects remained disorganized and was markedly thinner than the adjacent fascia. The results of this study suggest that SIS is capable of supporting tissue regeneration in large fascial defects. The ability of this material to induce regeneration of a substantial area of tissue grossly and histologically similar to normal fascia and without adhesions to the underlying musculature makes its application in reconstructive surgery appear promising.

Animals↗
PubMed1997

A combination of insulin-like growth factor-I and platelet-derived growth factor enhances myelination but diminishes axonal regeneration into Schwann cell grafts in the adult rat spinal cord.

Insulin-like growth factor-I (IGF-I) promotes axonal regeneration in the peripheral nervous system and this effect is enhanced by platelet-derived growth factor (PDGF). We decided, therefore, to study the effects of these factors on axonal regeneration in the adult rat spinal cord. Semipermeable polymer tubes, closed at the distal end, containing Matrigel mixed with cultured rat Schwann cells and IGF-I/PDGF, were placed at the proximal stump of the spinal cord after removal of the thoracic T9-11 segments. Control animals received implants of only Matrigel and Schwann cells or only Matrigel and IGF-I/PDGF. Four weeks after implantation, electron microscopic analysis showed that the addition of IGF-I/PDGF resulted in an increase in the myelinated:unmyelinated fiber ratio from 1:7 to 1:3 at 3 mm in the Schwann cell graft, and that myelin sheath thickness was increased 2-fold. The reduced number of unmyelinated axons was striking in electron micrographs. These results suggested that IGF-I/PDGF enhanced myelin formation of regenerated axons in Schwann cell implants, but there was a 36% decrease in the total number of myelinated axons at the 3 mm level of the graft. This finding and the altered myelinated:unmyelinated fiber ratio revealed that the overall fiber regeneration into Schwann cell implants was diminished up to 63% by IGF-I/PDGF. Histological evaluation revealed that there were more larger cavities in tissue at the proximal spinal cord-graft interface in animals receiving a Schwann cell implant with IGF-I/PDGF. Such cavitation might have contributed to the reduction in axonal ingrowth. In sum, the results indicate that whereas the combination of IGF-I and PDGF enhances myelination of regenerating spinal cord axons entering implants of Matrigel and Schwann cells after midthoracic transection, the overall regeneration of axons into such Schwann cell grafts is diminished.

Animals↗
PubMed1996

Inferior functional sensory regeneration after suture of sciatic neurotomy in newborns compared with mature rats.

It is generally believed that nerve injuries in children regenerate better than those which occur in adults. However, there are no functional experimental studies that support this belief. This study evaluates the functional regeneration of polymodal C-fibres after nerve regeneration in newborn and mature rats 3 months after unilateral sciatic nerve neurotomy and suture. The distribution of polymodal C-fibres was tested by measuring the Evans blue-stained area in the skin after antidromic nerve stimulation. In the newborn group of regenerated animals showed that functional C-fibres were present in a significantly (P < 0.05) smaller area than found in the adult group. We conclude that the functional regeneration of C-fibres is superior in mature rats compared with newborns, 3 months after regeneration.

Age Factors↗
PubMed2000

Nerve repair by means of vein filled with muscle grafts. II. Morphological analysis of regeneration.

The morphological features of regeneration in long-distance (3 cm) muscle-vein-combined grafts were experimentally investigated in the rat sciatic nerve by means of light and electron microscopy. In the early phases of regeneration (14 days after surgery), many regenerating nerve fibers were detected along the muscle-vein-combined graft. Six months after surgery, quantitative morphometrical analysis of myelinated nerve fibers showed that both the total number and density of myelinated nerve fibers were significantly greater in regenerated nerves than in control nerves. The contrary appeared true for the mean fiber size, with fiber size significantly smaller in regenerated nerves. Ultrastructural observations allowed the description of some peculiar aspects of the relationship between muscle fibers, nerve fibers, and Schwann cells in both early and late phases of regeneration.

Animals↗
PubMed1999

Two Nkx-3-related genes are expressed in the adult and regenerating central nervous system of the urodele Pleurodeles waltl.

We report the isolation and characterization of two NK-3-related genes (PwNkx-3.2 and PwNkx-3.3) and their expression patterns during embryonic development, in the adult CNS, and during tail regeneration in the urodele Pleurodeles waltl. PwNkx-3.2 is the ortholog of the mouse and Xenopus genes, Bapx 1 and Xbap, but PwNkx-3.3 has no known homologue in any other vertebrate. We demonstrate that PwNkx-3.2 and PwNkx-3.3 exhibit graded axial expression patterns in adult spinal cord. During tail regeneration, the two genes are expressed in the wound epidermis, the regenerating muscle masses, the regenerating neural tube, the spinal ganglia, and the cartilage rod. The spatial distribution of transcripts in the CNS suggests that these genes could participate in maintaining the position information along the anteroposterior axis and may explain the ability of the adult CNS to regenerate. During tail regeneration, both genes could be implicated in the reformation of the axial skeleton.

Amino Acid Sequence↗
PubMed2001

Evidence for two distinct mechanisms of neurogenesis and cellular pattern formation in regenerated goldfish retinas.

After its destruction by intraocular injection of ouabain, the goldfish retina regenerates, but little is known about the histogenesis of the new tissue, including the structure and formation of regenerated cell mosaic patterns. In an effort to determine how retinal cells are generated and spatially organized within retina regenerated after ouabain injection, in situ hybridization and immunocytochemical techniques were combined with computational analyses of two-dimensional spatial patterns of identified neurons. Labeling with specific opsin riboprobes revealed two distinct cone patterns in the ouabain-injected eyes, each of which was different from the relatively orderly cone patterns of native retina. Central, regenerated regions had sparse aggregates of cones, and a relatively lower density of each cone type. Peripheral regions of experimental retina, likely derived from the circumferential germinal zone, had high densities of all cone types, each of which tended to be distributed randomly. The spatial patterns of inner retinal neurons in experimental eyes were also disorganized with respect to native retina. These results indicate that although some aspects of retinal regeneration resemble normal retinal development and growth, ouabain-induced regeneration does not produce well-organized mosaics of neurons, indicating a failure of the developmental interactions needed for proper pattern formation, which in turn could compromise visual recovery. Furthermore, the distinct cone patterns in different regions of experimental retina support the hypothesis that new goldfish retina arises via two spatially and cellularly distinct mechanisms after exposure to ouabain.

Animals↗