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PubMed2006

Wnt/beta-catenin signaling regulates vertebrate limb regeneration.

The cellular and molecular bases allowing tissue regeneration are not well understood. By performing gain- and loss-of-function experiments of specific members of the Wnt pathway during appendage regeneration, we demonstrate that this pathway is not only necessary for regeneration to occur, but it is also able to promote regeneration in axolotl, Xenopus, and zebrafish. Furthermore, we show that changes in the spatiotemporal distribution of beta-catenin in the developing chick embryo elicit apical ectodermal ridge and limb regeneration in an organism previously thought not to regenerate. Our studies may provide valuable insights toward a better understanding of adult tissue regeneration.

Ambystoma↗
PubMed1994

Are Schwann cells essential for axonal regeneration into muscle autografts?

When axons regenerate through frozen-thawed (FT) muscle grafts, they are accompanied by co-migrating Schwann cells derived from the nerve stumps. Although acellular, FT muscle grafts contain an internal scaffold of basal laminae rich in components capable of supporting neurite outgrowth in vitro such as laminin and fibronectin: it is not known whether Schwann cells are essential for axonal regrowth within these grafts. In this paper we test the hypothesis that sarcolemmal basal laminae will support axonal regeneration in the absence of Schwann cells. Two groups of 12 adult Wistar rats were used. All rats received a 0.5 cm FT muscle graft, and 12 rats also received a subperineurial injection of the anti-mitotic agent mitomycin C (400 micrograms/ml in physiological saline) prior to grafting. Previous studies have shown that this dose effectively depresses cell proliferation within the endoneurium for 3-4 weeks [17, 18, 28]. Rats were killed (n = 3) 1, 2, 3 or 4 weeks later. The spatio-temporal sequence of axonal regeneration into the grafts was assessed histologically, by immunofluorescence using antibodies against GAP-43; S-100; RT97; laminin and macrophages (ED1), and by transmission electron microscopy. Outgrowth of almost all axons from the mitomycin C-treated proximal stumps was delayed for up to 3 weeks, after which time vigorous regeneration occurred into the persisting tubes of sarcolemmal basal lamina. All axons regenerating within the grafts (irrespective of mitomycin C-treatment) were accompanied by co-migrating Schwann cells. The results suggest that Schwann cells play an important role in axonal regeneration across FT muscle autografts and that sarcolemmal basal laminae alone are insufficient to support axonal regeneration.

Animals↗
PubMed1986

Studies on polypeptide composition, hydrolytic activity and proton conduction of mitochondrial FoF1 H+ ATPase in regenerating rat liver.

A study of the FoF1 ATPase complex of mitochondria isolated from regenerating rat liver following partial (70%) hepatectomy is presented. As we have previously reported, ATPase activity in submitochondrial particles prepared from regenerating rat liver 24 h following partial hepatectomy was depressed by 75% with respect to controls (submitochondrial particles from sham-operated animals). Polyacrylamide gel electrophoresis and immunodecoration using an antibody raised against isolated bovine heart F1 sector of the FoF1 ATPase indicated a substantial decrease in F1 content in the mitochondrial membrane from regenerating rat liver. Proton conduction by the FoF1 ATPase complex was studied by following the anaerobic relaxation of the transmembrane proton gradient (delta mu H+) generated by succinate-driven respiration. In control rat-liver submitochondrial particles containing the FoF1 moiety of the ATPase complex, anaerobic relaxation of delta mu H+ showed biphasic kinetics, whilst the same process in particles derived from regenerating rat liver exhibited monophasic kinetics and was significantly more rapid. Oligomycin and N,N-dicyclohexyl carbodiimide [(cHxN)2C] inhibited proton conductance by the F1-Fo ATPase complex in submitochondrial particles from both control and regenerating rat liver. Binding of [14C](cHxN)2C and immunodecoration using an antibody raised against bovine heart oligomycin-sensitivity-conferring protein (OSCP) indicated no difference in the content of either the (cHxN)2C binding protein or OSCP between control and regenerating rat-liver mitochondrial membranes. The results reported show that the structural and functional integrity of the Fo-F1 ATPase of rat liver is severely perturbed during regeneration.

Adenosine Triphosphatases↗
PubMed1999

Modality-specific hyper-responsivity of regenerated cat cutaneous nociceptors.

1. Experiments were performed on anaesthetized cats to investigate the receptive properties of regenerated cutaneous tibial nerve nociceptors, and to obtain evidence for coupling between them and other afferent fibres as being possible peripheral mechanisms involved in neuropathic pain. These properties were studied 6-7 months after nerve section and repair. 2. Recordings were made from 25 regenerated nociceptors; 14 were A fibres and the remainder were C fibres. Their receptive field sizes and conduction velocities were similar to controls. There was no significant difference between their mechanical thresholds and those of a control population of nociceptors. 3. Regenerated nociceptors were significantly more responsive to suprathreshold mechanical stimuli than were uninjured control fibres. This increase in mechanical sensitivity occurred in both A and C fibres, although A fibres showed a greater increase in mechano-sensitivity than C fibres. Over half of the regenerated nociceptors (13/25) showed after-discharge to mechanical stimuli which was never seen in controls; the mean firing rate during this period of after-discharge was significantly related to both stimulus intensity and stimulus area. 4. There was no significant difference between the heat encoding properties of regenerated nociceptors and control nociceptors. Cold sensitivity was similarly unchanged. Thus, abnormal peripheral sprouting was unlikely to account for the increased mechanical sensitivity of the regenerated fibres. None of the regenerated nociceptors were found to be coupled to other fibres. 5. These results suggest that the clinical observation of mechanical hyperalgesia in patients after nerve injury may have a peripheral basis. Based on this model, other signs of neuropathic pain (i.e. tactile or thermal allodynia) are more likely to be due to altered central processing.

Anesthesia↗
PubMed1992

Effects of alcohol feeding on synthesis and secretion of apolipoproteins by regenerating rat sciatic nerve.

The amounts of apolipoprotein (apo) E and A1 released into the culture medium were examined in the regenerating nerves distal to a crush site following chronic alcohol feeding. Cultured minced segments of regenerating nerves taken from rats fed an alcohol-containing liquid diet for 5 weeks released only 50% of apoE but nearly 200% of apoA1 when compared with rats pair-fed with a control diet. The extent of decrease in medium apoE corresponded to the decrease of apoE mRNA in the nerve. Thus, chronic alcohol ingestion affects apoE synthesis of regenerating nerves by changing its mRNA level. On the other hand, apoA1 mRNA remained undetectable in regenerating and intact nerves whether the rats were fed alcohol or not. Furthermore, the amount of apoA1 released by the regenerating nerve into the culture medium was not significantly larger than that present in the nerve tissue prior to incubation. Therefore, it is most likely that apoA1 released by the injured nerve originated from the bloodstream and the increase in apoA1 content seen in the crushed nerve of alcohol-fed rats is due to an enhanced permeability of the nerve-blood barrier. Since the burst of apolipoproteins in the injured nerve is likely to play a role in nerve regeneration, the perturbation of apolipoprotein contents in regenerating nerves by chronic alcohol consumption may contribute to the pathogenesis of alcoholic neuropathy.

Alcoholism↗
PubMed2005

Prognostic factors for alveolar regeneration: effect of space provision.

OBJECTIVES: The role of space provision as an independent prognostic factor for periodontal regeneration remains to be established. The objective of this study was to evaluate the role of space provision on alveolar bone regeneration in periodontal sites. METHODS: Critical size, supra-alveolar, periodontal defects were created in 11 young adult Beagle dogs. Six animals received a porous ePTFE device to provide for space provision. Five animals received sham surgery. The animals were euthanized at 8 weeks post-surgery. A histometric analysis assessed vertical regeneration of alveolar bone and the width of the alveolar crest at the base of the defect. Because of the correlation of within-dog measurements, a mixed model anova/ancova was used to analyse the data. RESULTS: A significant relationship between the width of the alveolar crest at the base of the defect and bone regeneration was observed with no significant difference between sites receiving the different treatments (p=0.84). Bone regeneration at sites treated with the space-providing device was significantly greater compared with that at sites treated with sham surgery (p=0.0003), and the difference remained significant after adjusting for bone width (p=0.0001). CONCLUSIONS: Space provision has a significant effect on alveolar bone regeneration in periodontal sites. The width of the alveolar bone appears to influence space provision effectively supporting bone regeneration.

Alveolar Bone Loss↗
PubMed2004

Willingness to pay for dentin regeneration in a sample of dentate adults.

OBJECTIVES: Measurement of individuals' valuation of dental treatments is important in the evaluation of new technologies. In this paper the value of dentin regeneration, a new treatment for teeth with reversible pulpitis, is measured based on what individuals say they would be willing to pay to receive the treatment. METHODS: A total of 611 randomly selected dentate adults answered willingness to pay (WTP) and dental insurance questions. Detailed descriptions of the process and expected outcomes for dentin regeneration were presented to subjects as part of a larger study measuring preferences for different treatments. WTP was determined for two different levels of success for dentin regeneration. RESULTS: At a success rate of 95%, the mean WTP for dentin regeneration was $262.70 (noninsured) and $11.00 per month (insured subjects). For success rate of 75%, the corresponding values were $210.90 and $9.20 per month. Multivariate analyses were used to identify any significant relationships between WTP and a range of variables covering socio-demographic, socio-economic, dental experience and oral health status variables. The findings indicate that individuals' valuations of treatments involve substantial unexplained variation. About half of the noninsured subjects would pay for dentin regeneration if it cost $200 per tooth. CONCLUSIONS: The data on the WTP for dentin regeneration indicate that a substantial percentage of adults will pay for this new technology. This study provides for the first time an estimate of WTP for dentin regeneration among the population.

Adult↗
PubMed1989

Preliminary evidence for pineal-mediated extraretinal photoreception in relation to tail regeneration in the Gekkonid lizard, Hemidactylus flaviviridis.

The tail of the Gekkonid lizard Hemidactylus flaviviridis was autotomized and the animals were subjected to eight different photoperiodic schedules during the process of tail regeneration. Our previous observation had shown that long-day photoperiods stimulate the regeneration process, whereas short-day photoperiods depress it. Furthermore, it has also been demonstrated that the lateral eyes, or retinae, do not participate in photoperiodically significant photoreception in H. flaviviridis, as blinded Hemidactylus regenerated their autotomized tails like their sighted counterparts exposed to similar experimental photoregimes. In a further attempt to localize the site(s) of photoreception in these animals, one group of lizards had their heads painted with a mixture of Indian ink and Nile blue sulphate (II-NBS) [NL (HP)] in order to prevent light from penetrating to the pineal gland, and another group had their pineal glands surgically removed (pinealectomy, Px); the regenerative potentials were compared with their normal (NL) counterparts. Our results showed that the initiation and onset of regeneration, the daily growth rate, the total new growth (regenerate) produced at the end of regeneration and the total percentage replacement of the lost (autotomized) tails were significantly retarded in Px and NL (HP) animals, compared with the NL (unoperated and nonpainted) ones. Since pinealectomy as well as light deprivation to the pineal abolished the stimulatory influence of long-length photoperiods, the pineal gland is discussed here as a major transmitter of photic stimulus in lacertilian tail regeneration. It is presumed that in the lizard, as in mammals and some birds, the pineal gland acts by way of the neuroendocrine complex and/or the hypothalamohypophyseal axis.

Animals↗
PubMed1987

Identification of trophic factors and transplanted cellular environments that promote CNS axonal regeneration.

As indicated in this review, we have begun to elucidate cellular environments and trophic factors that promote the regeneration of adult mammalian CNS neurons. In the present paradigm, bilateral aspiration lesions of the fornix-fimbria are used to axotomize septal neurons and transect the septal cholinergic projection to the dorsal hippocampus in order to evaluate the influence of trophic factors, such as NGF, on neuronal survival and the ability of cellular transplants of PNS tissue to promote axonal regeneration in vivo. Initial results demonstrate that NGF is a potent trophic molecule that prevents retrograde degeneration of septal cholinergic neurons. Observations from transplantation studies demonstrate that viable Schwann cells obtained from PNS nerve grafts or Schwann cell-ECM cultures provide a favorable cellular milieu for CNS regeneration. These cellular transplants induce a remarkable sprouting response from septal cholinergic neurons and promote the rapid elongation of septal axons that reinnervate the denervated hippocampus. In stark contrast to the Schwann cell-laden transplants, transplants including only ECM channels synthesized by cultured Schwann cells do not promote axonal regeneration within the time periods that we have examined. Therefore, we hypothesize that viable Schwann cells are crucial for the process of regeneration because they contribute both trophic and tropic factors to the injured CNS neurons. The significant early sprouting phenomenon associated with transplants containing Schwann cells strongly suggests that soluble Schwann cell-synthesized factors induce axon elongation and possibly enhance the survival of injured septal neurons. The trophic factors probably function in a manner similar, if not identical, to the action of NGF on axotomized septal neurons. Moreover, Schwann cells appear to provide tropic signals, such as LAM or a LAM-NGF complex, that can act, when in the proper stereoconfiguration, to promote the elongation and orientation of regenerating axons. Thus, our current data indicate that in order to promote optimal axonal regeneration from injured CNS neurons, both trophic and tropic factors must be supplied from exogenous sources.

Animals↗
PubMed1978

Kinetics of bleaching and regeneration of rhodopsin in abnormal (RCS) and normal albino rats in vivo.

1. Rhodopsin concentration has been measured by the method of densitometry in retinae of rats with inherited retinal dystrophy (RCS) raised in darkness and compared with that of normal rats similarly reared. 2. In both RCS and normal rats the fraction of rhodopsin bleached is always directly proportional to the photon content of the light, I.t, where I is the light intensity in effective quanta (500 nm) cm-2 sec-1 and t is the duration of the bleaching exposure in seconds. 3. Rhodopsin photosensitivity for bleaching is slightly higher in RCS rats than in normals (2.3 (10)-16 cm2 chromophore-1 compared with 1.3 (10)-16 cm2 chromophore-1). 4. Rhodopsin regeneration in the dark in both RCS and normal rats cannot be described by the kinetics of a simple monomolecular chemical reaction. 5. Following 5 min bleaches, the regeneration rate becomes slower as the preceding bleach is made stronger. Regeneration in the dark is significantly faster in the RCS rats than in the normal ones. 6. In normal rats, after a full bleach, rhodopsin regenerates back to the dark-adapted level within 3--4 hr. In RCS rats rhodopsin regenerates to reach a plateau level, below the previous dark-adapted level, that lasts for several hours. 7. The faction of total rhodopsin that can regenerate gradually declines with age until in 70 days old RCS rats no rhodopsin regeneration can be measured by the ensitometer. However, total rhodopsin density (fully bleached-dark-adapted) is still close to normal.

Age Factors↗
PubMed1991

Neuromuscular transmission at newly formed neuromuscular junctions in the regenerating soleus muscle of the rat.

1. A study of neuromuscular function in regenerating skeletal muscle fibres in the rat soleus muscle has been made. The muscle fibres were damaged in vivo by the injection of the myotoxic venom component notexin, and then allowed to regenerate spontaneously. 2. Regenerating muscle fibres generated action potentials and contracted following direct intracellular stimulation as early as 4 days after the injection of notexin. 3. Miniature endplate potentials (MEPPs) were recorded at a minority of synapses at 3 days, and from all synapses by 5 days. The mean amplitude of MEPPs in a given fibre was directly proportional to muscle fibre input resistance. 4. Spontaneous transmitter release in the regenerating fibres was relatively insensitive to changes in [K+]0 but the effect of Ruthenium Red on spontaneous release was similar in the regenerating and control muscle fibres. 5. Functional innervation, defined as the ability to generate an indirect action potential, was restored in 97% of fibres by 10 days. The generation of an action potential was always associated with a twitch of the muscle fibre. Those fibres that were unable to generate an action potential usually exhibited a low membrane potential (ca -50 mV). These fibres could generate action potentials if they were hyperpolarized using an intracellular current-passing microelectrode. 6. The quantal content of endplate potentials (EPPs) was estimated from the mean EPP and mean MEPP amplitudes in cut muscle fibre preparations. These estimates suggested that quantal content was low at the earliest stages of regeneration, but increased as the muscle fibres matured and became normal at 10-21 days. 7. During repetitive stimulation at 30 Hz there was a fall in the amplitude of EPPs of 40-45%. The fall was similar in regenerating and control fibres. Conducting synapses never exhibited failure to generate an EPP during the period of high-frequency stimulation.

Action Potentials↗
PubMed2005

fgf20 is essential for initiating zebrafish fin regeneration.

Epimorphic regeneration requires the presence or creation of pluripotent cells capable of reproducing lost organs. Zebrafish fin regeneration is mediated by the creation of blastema cells. Here, we characterize the devoid of blastema (dob) mutant that fails fin regeneration during initial steps, forms abnormal regeneration epithelium, and does not form blastema. This mutation has no impact on embryonic survival. Dob results from an fgf20a null mutation, Y148S. Fgf20a is expressed during initiation of fin regeneration at the epithelial-mesenchymal boundary and later overlaps with the blastema marker msxb. Thus, fgf20a has a regeneration-specific requirement, initiating fin regeneration, and controlling blastema formation.

Animals↗
PubMed1996

Asialo GM1 is a receptor for Pseudomonas aeruginosa adherence to regenerating respiratory epithelial cells.

We investigated the implication of asialo GM1 as an epithelial receptor in the increased Pseudomonas aeruginosa affinity for regenerating respiratory epithelial cells from cystic fibrosis (CF) and non-CF patients. Human respiratory epithelial cells were obtained from nasal polyps of non-CF subjects and of CF patients homozygous for the delta F 508 transmembrane conductance regulator protein (CFTR) mutation and cultured according to the explant-outgrowth model. At the periphery of the outgrowth, regenerating respiratory epithelial cells spreading over the collagen I matrix with lamellipodia were observed, characteristic of respiratory epithelial wound repair after injury. P aeruginosa adherence to regenerating respiratory epithelial cells was found to be significantly greater in the delta F 508 homozygous CF group than in the non-CF group (P < 0.001). In vitro competitive binding inhibition assays performed with rabbit polyclonal antibody against asialo GM1 demonstrated that blocking asialo GM1 reduces P. aeruginosa adherence to regenerating respiratory epithelial cells in delta F 508 homozygous cultures (P < 0.001) as well as in non-CF cultures (P < 0.001). Blocking of asialo GM1 was significantly more efficient in CF patients than in non-CF subjects (P < 0.05). Distribution of asialo GM1 as determined by preembedding labelling and immunoelectron microscopy clearly demonstrated the specific apical membrane expression of asialo GM1 by regenerating respiratory epithelial cells, whereas other cell phenotypes did not apically express asialo GM1. These results demonstrate that (i) asialo GM1 is an apical membrane receptor for P. aeruginosa expressed at the surface of CF and non-CF regenerating respiratory epithelial cells and (ii) asialo GM1 is specifically recovered in regenerating respiratory epithelium. These results suggest that in CF, epithelial repair represents the major event which exposes asialo GM1 for P. aeruginosa adherence.

Adolescent↗
PubMed1990

c-myc, c-fos, and c-jun regulation in the regenerating livers of normal and H-2K/c-myc transgenic mice.

We investigated the mechanisms of regulation of c-myc, c-fos, and c-jun at the early stages of liver regeneration in mice. We show that the transient increase in steady-state levels of c-myc mRNA at the start of liver regeneration is most probably regulated by posttranscriptional mechanisms. Although there was a marked increase in c-myc transcriptional initiation shortly after partial hepatectomy, a block in elongation prevented the completion of most transcripts. To gain further information on the mechanism of regulation of c-myc expression during liver regeneration, we used transgenic mice harboring the human c-myc gene driven by the H-2K promoter. In these animals, the murine c-myc responded to the growth stimulus generated by partial hepatectomy, whereas the expression of the transgene was constitutive and did not change in the regenerating liver. However, the mRNA from both genes increased markedly after cycloheximide injection, suggesting that the regulation of c-myc mRNA abundance in the regenerating liver differs from that occurring after protein synthesis inhibition. Furthermore, we show that in normal mice c-fos and c-jun mRNA levels and transcriptional rates increase within 30 min after partial hepatectomy. c-fos transcriptional elongation was restricted in nongrowing liver, but the block was partially relieved in the regenerating liver. Nevertheless, for both c-fos and c-jun, changes in steady-state mRNA detected after partial hepatectomy were much greater than the transcriptional increase. In the regenerating liver of H-2K/c-myc mice, c-fos and c-jun expression was diminished, whereas mouse c-myc expression was enhanced in comparison with that in nontransgenic animals.

Animals↗
PubMed1991

The gene encoding rat insulinlike growth factor-binding protein 1 is rapidly and highly induced in regenerating liver.

The liver is an epithelioid organ that can regenerate following partial hepatectomy. Although it is composed mainly of hepatocytes, it has a complex, multicellular architecture, implying that intercellular communications must exist during regeneration. As in other mitogen-stimulated cells, immediate-early growth response genes induced in the absence of prior protein synthesis are likely to play an important regulatory role in the regenerative process. Through differential screening of regenerating liver cDNA libraries, we found that one of the most highly expressed immediate-early genes in liver regeneration encodes the rat homolog of the low-molecular-weight insulinlike growth factor (IGF)-binding protein (IGFBP-1). This protein has been implicated in enhancing the mitogenic effect of IGF on tissues. IGFBP-1 gene induction is transcriptionally mediated and specific to regenerating liver, as the gene is not expressed in mitogen-stimulated fibroblasts. IGFBP-1 expression has been shown to increase under low-insulin conditions such as diabetes, and the complex regulation of expression is indicated by our finding that insulin treatment of H35 rat hepatoma cells, which induces proliferation, also causes a rapid decrease in transcription and expression of the IGFBP-1 gene. Of note, IGFBP-1 mRNA is abundant in fetal rat liver, implying that it participates in normal liver growth and development. Although regenerating liver cells continue to produce IGF-I, we did not detect IGF-I receptor mRNA during the first 24 h after hepatectomy. However, some IGFBPs may act to enhance the activity of IGF-I independently of IGF-I receptors. Thus, IGF-1 and IGFBPs may interact with hepatocytes or nonparenchymal liver cells, through either IGF-I or novel receptors. In this way, IGFBP-I and IGF-I could act in a paracrine and/or autocrine fashion in maintaining normal liver architecture during regeneration.

Amino Acid Sequence↗
PubMed1999

Premature expression of the winged helix transcription factor HFH-11B in regenerating mouse liver accelerates hepatocyte entry into S phase.

Two-thirds partial hepatectomy (PH) induces differentiated cells in the liver remnant to proliferate and regenerate to its original size. The proliferation-specific HNF-3/fork head homolog-11B protein (HFH-11B; also known as Trident and Win) is a family member of the winged helix/fork head transcription factors and in regenerating liver its expression is reactivated prior to hepatocyte entry into DNA replication (S phase). To examine whether HFH-11B regulates hepatocyte proliferation during liver regeneration, we used the -3-kb transthyretin (TTR) promoter to create transgenic mice that displayed ectopic hepatocyte expression of HFH-11B. Liver regeneration studies with the TTR-HFH-11B mice demonstrate that its premature expression resulted in an 8-h acceleration in the onset of hepatocyte DNA replication and mitosis. This liver regeneration phenotype is associated with protracted expression of cyclin D1 and C/EBPbeta, which are involved in stimulating DNA replication and premature expression of M phase promoting cyclin B1 and cdc2. Consistent with the early hepatocyte entry into S phase, regenerating transgenic livers exhibited earlier expression of DNA repair genes (XRCC1, mHR21spA, and mHR23B). Furthermore, in nonregenerating transgenic livers, ectopic HFH-11B expression did not elicit abnormal hepatocyte proliferation, a finding consistent with the retention of the HFH-11B transgene protein in the cytoplasm. We found that nuclear translocation of the HFH-11B transgene protein requires mitogenic signalling induced by PH and that its premature availability in regenerating transgenic liver allowed nuclear translocation to occur 8 h earlier than in wild type.

Animals↗
PubMed1987

Hormone action in newt limb regeneration: insulin and endorphins.

Although several hormones have been linked to newt limb regeneration, a cohesive hypothesis as to how these hormones control the process is yet to emerge. A critical review of the traditional approaches and a reevaluation of currently operative assumptions and interpretations of results precede the data on insulin and beta-endorphin. Results from in vivo and in vitro experiments on insulin are summarized, showing that insulin not only promotes various cellular events but also is essential for the expression of the mitogenic effect of nerves on cultured newt limb blastemata. Furthermore, the strong likelihood that insulin may be the common link in promoting limb regeneration in hypophysectomized newts that received pituitary hormone replacement therapy or a nutritional supplement is discussed. The status of beta-endorphin in regeneration is also explored. Data are presented to show that vertebrates with regenerating capacity (newts, tadpoles) have higher levels of plasma beta-endorphin than that found in species where the capacity to regenerate is either restricted (frogs) or totally lost (mammals). beta-Endorphin-like immunoreactivity has been localized in the epidermis of a regenerating newt blastema, as well as in the intermediate lobe of the pituitary gland of axolotl, newt, and Xenopus. A possible opiate connection in vertebrate limb regeneration, in particular, wound healing, is discussed.

Animals↗
PubMed1987

Use of retinoids to analyze the cellular basis of positional memory in regenerating amphibian limbs.

Cells of the amphibian limb regeneration blastema inherit memories of their level of origin (positional memory) along the limb axes. These memories serve as boundaries of what is to be regenerated, thus preventing regeneration of any but the missing structures. Because of its importance in determining the boundaries of regenerate pattern, it is essential to understand the cellular and molecular basis of positional memory. One approach to this problem is to look for position-related differences in a cell or molecular property along a limb axis and then show, using an agent that modifies regenerate pattern, that the cell or molecular property and the pattern are coordinately modified. We have done this using retinoic acid (RA) as a pattern-modifying agent and an in vivo assay that detects position-related differences in a cell recognition-affinity property along the proximodistal (PD) axis of the regenerating axolotl limb. RA proximalizes positional memory in the PD axis, posteriorizes it in the anteroposterior axis, and ventralizes it in the dorsoventral axis. The level-specific PD cell recognition-affinity property is proximalized by RA, indicating that this property and positional memory are causally related. The effects of RA on positional memory may be mediated through a cellular RA-binding protein (CRABP), since the concentration of unbound (apo) CRABP molecules is highest during early stages of regeneration when the proximalizing effects of RA are greatest.

Amphibians↗