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PubMed1996

Developmental regulation of two distinct neuronal phenotypes in rat dorsal root ganglia.

In a previous study we described two distinct neuronal phenotypes in rat dorsal root ganglia based on immunocytochemical assays for the neuronal intermediate filament proteins, peripherin and low-molecular-weight neurofilaments [Goldstein M. E. et al. (1991) J. Neurosci. Res. 30, 92-104]. In this paper we have extended this classification by using in situ hybridization to localize and evaluate the levels of various cytoskeletal and neuropeptide messenger RNAs within the peripherin-immunoreactive and peripherin-immunoreactive-negative neurons found in embryonic day 15 and 20, postnatal day 2 and adult dorsal root ganglia. We found in postnatal and adult dorsal root ganglia in vivo that the large, peripherin-immunoreactive-negative neurons, which are intensely stained by low-molecular-weight neurofilament antibodies, also contain high levels of low, medium and high-molecular-weight neurofilament messenger RNAs, whereas the smaller peripherin-immunoreactive neurons do not. On the other hand, both cell types contained comparable levels of peripherin and alpha-tubulin messenger RNA. The presence of peripherin messenger RNA but no peripherin immunoreactivity in the large cells suggested either a translational or post-translational regulation of this polypeptide, or rapid clearance of this protein from the perikaryon into the axon. In adult dorsal root ganglia, more than 50% of the peripherin-immunoreactive neurons also contained high levels of substance P and/or calcitonin gene-related peptide messenger RNAs, while less than 20% of the large peripherin-immunoreactive-negative neurons did. The attainment of these phenotypic characteristics during development in vivo was studied by northern blot and in situ hybridization histochemistry. In early embryonic stages (embryonic days 15-16), virtually all neurons were peripherin-immunoreactive and were positive for peripherin, alpha-tubulin and low-molecular-weight neuro-filament messenger RNAs, suggesting a homogeneous population. By embryonic day 20, the two adult phenotypes became clearly evident, and were fully established by postnatal day 2. In cultures of embryonic day 15 dorsal root ganglion neurons grown in the presence of nerve growth factor, peripherin and low-molecular-weight neurofilament messenger RNAs were expressed in all neurons, even after nine days in vitro, similar to embryonic dorsal root ganglia in vivo. Nerve growth factor supplemented by skeletal and heart muscle extracts did up-regulate neurofilament gene expression, but not to the extent characteristic of the peripherin-immunoreactive-negative adult phenotype. These results suggest that development of the mature phenotype of dorsal root ganglion neurons occurs by postnatal day 2 in vivo and is dependent upon target contact and/or target-derived factors.

Animals↗
PubMed2003

A role for intermediate filaments in determining and maintaining the shape of nerve cells.

To date, the functions of most neural intermediate filament (IF) proteins have remained elusive. Peripherin is a type III intermediate filament (IF) protein that is expressed in developing and in differentiated neurons of the peripheral and enteric nervous systems. It is also the major IF protein expressed in PC12 cells, a widely used model for studies of peripheral neurons. Dramatic increases in peripherin expression have been shown to coincide with the initiation and outgrowth of axons during development and regeneration, suggesting that peripherin plays an important role in axon formation. Recently, small interfering RNAs (siRNA) have provided efficient ways to deplete specific proteins within mammalian cells. In this study, it has been found that peripherin-siRNA depletes peripherin and inhibits the initiation, extension, and maintenance of neurites in PC12 cells. Furthermore, the results of these experiments demonstrate that peripherin IF are critical determinants of the overall shape and architecture of neurons.

Animals↗
PubMed1998

Distribution of neuronal intermediate filament proteins in the developing mouse olfactory system.

The distribution of neuronal intermediate filament proteins in the developing mouse olfactory bulb and olfactory epithelium was characterized by immunocytochemical approach. Antibodies against alpha-internexin, neurofilament triplet proteins (NFTPs; NF-L, NF-M, and NF-H) and peripherin were used to determine their expression at different developmental stages. Alpha-internexin and peripherin were first found to be co-localized in the olfactory neuroepithelium during early development. At the perinatal stage, expression patterns of alpha-internexin and peripherin are distinguishable by spatial and temporal manner: peripherin is predominantly expressed in the olfactory nerves; whereas alpha-internexin is expressed in both olfactory nerves and olfactory bulb. Our observation suggests that peripherin as well as alpha-internexin may play some roles in the process formation of olfactory nerves during development. In the developing olfactory periglomerulus, alpha-internexin was found around postnatal Day 3, whereas NFTPs were not observed until postnatal Day 7. Our data showed that the expression of alpha-internexin preceded those of the NFTPs in most neurons of the developing olfactory bulb. Some small neurons in the adult olfactory bulb were uniquely labeled with antibody to alpha-internexin. Our results suggest that alpha-internexin may play a functional role in the neuronal cytoarchitecture of developing olfactory system, and can be a neuronal marker for detecting postmitotic migrating neurons in the adult olfactory bulb.

Animals↗
PubMed2001

Differential expression and localization of neuronal intermediate filament proteins within newly developing neurites in dissociated cultures of Xenopus laevis embryonic spinal cord.

The molecular subunit composition of neurofilaments (NFs) progressively changes during axon development. In developing Xenopus laevis spinal cord, peripherin emerges at the earliest stages of neurite outgrowth. NF-M and XNIF (an alpha-internexin-like protein) appear later, as axons continue to elongate, and NF-L is expressed after axons contact muscle. Because NFs are the most abundant component of the vertebrate axonal cytoskeleton, we must understand why these changes occur before we can fully comprehend how the cytoskeleton regulates axon growth and morphology. Knowing where these proteins are localized within developing neurites and how their expression changes with cell contact is essential for this understanding. Thus, we examined by immunofluorescence the expression and localization of these NF subunits within dissociated cultures of newly differentiating spinal cord neurons. In young neurites, peripherin was most abundant in distal neuritic segments, especially near branch points and extending into the central domain of the growth cone. In contrast, XNIF and NF-M were usually either absent from very young neurites or exhibited a proximal to distal gradient of decreasing intensity. In older neurites, XNIF and NF-M expression increased, whereas that of peripherin declined. All three of these proteins became more evenly distributed along the neurites, with some branches staining more intensely than others. At 24 h, NF-L appeared, and in 48-h cultures, its expression, along with that of NF-M, was greater in neurites contacting muscle cells, arguing that the upregulation of these two subunits is dependent on contact with target cells. Moreover, this contact had no effect on XNIF or peripherin expression. Our findings are consistent with a model in which peripherin plays an important structural role in growth cones, XNIF and NF-M help consolidate the intermediate filament cytoskeleton beginning in the proximal neurite, and increased levels of NF-L and NF-M help further solidify the cytoskeleton of axons that successfully reach their targets.

Animals↗
PubMed2002

Molecular probes of the vestibular nerve. II. Characterization of neurons in Scarpa's ganglion to determine separate populations within the nerve.

An unambiguous delineation of the exact numbers and/or proportions of calyx-only, dimorph, and bouton-only vestibular afferents is needed to continue studies concerning vestibular integration in the nervous system. Here, we take advantage of immunocytochemical properties of three groups of vestibular afferents. We utilize calretinin to delineate the calyx-only population, and peripherin to stain the bouton-only afferents. An additional subgroup of afferents that stain with calbindin, but not calretinin is also introduced. The size of the cells that stain with these markers was determined. Cells that are calbindin-positive overlap the sizes of Nissl-stained somata. Cells that stain with peripherin or calretinin are non-overlapping with calretinin cells being the largest and peripherin-positive cells the smallest. Twenty percent of the ganglion cells were peripherin positive, another 20% stained with calretinin antibodies, 30% stained with calbindin, and all cells in Scarpa's ganglion stained with parvalbumin. Most of the calretinin-positive cells also stained with calbindin. One-third of the calbindin-positive population stained only with calbindin. These studies indicate that the calyx- and bouton-only populations of vestibular afferents in gerbil comprise at least 40% of the nerve. In addition, at least 10% of the nerve also stains with calbindin and neither calretinin nor peripherin. Based on indirect evidence, we hypothesize that these are a subpopulation of dimorph afferents. This study has provided an anatomical instrument (in addition to intracellular physiological methods) to study separate populations of vestibular afferents.

Action Potentials↗
PubMed2006

Assembling an intermediate filament network by dynamic cotranslation.

We have been able to observe the dynamic interactions between a specific messenger RNA (mRNA) and its protein product in vivo by studying the synthesis and assembly of peripherin intermediate filaments (IFs). The results show that peripherin mRNA-containing particles (messenger ribonucleoproteins [mRNPs]) move mainly along microtubules (MT). These mRNPs are translationally silent, initiating translation when they cease moving. Many peripherin mRNPs contain multiple mRNAs, possibly amplifying the total amount of protein synthesized within these "translation factories." This mRNA clustering is dependent on MT, regulatory sequences within the RNA and the nascent protein. Peripherin is cotranslationally assembled into insoluble, nonfilamentous particles that are precursors to the long IF that form extensive cytoskeletal networks. The results show that the motility and targeting of peripherin mRNPs, their translational control, and the assembly of an IF cytoskeletal system are linked together in a process we have termed dynamic cotranslation.

Animals↗
PubMed2003

Rapid transport of neural intermediate filament protein.

Peripherin is a neural intermediate filament protein that is expressed in peripheral and enteric neurons, as well as in PC12 cells. A determination of the motile properties of peripherin has been undertaken in PC12 cells during different stages of neurite outgrowth. The results reveal that non-filamentous, non-membrane bound peripherin particles and short peripherin intermediate filaments, termed 'squiggles', are transported at high speed throughout PC12 cell bodies, neurites and growth cones. These movements are bi-directional, and the majority require microtubules along with their associated molecular motors, conventional kinesin and cytoplasmic dynein. Our data demonstrate that peripherin particles and squiggles can move as components of a rapid transport system capable of delivering cytoskeletal subunits to the most distal regions of neurites over relatively short time periods.

Animals↗
PubMed2005

Cytoskeletal defects in amyotrophic lateral sclerosis (motor neuron disease).

There is growing evidence for the involvement of cytoskeletal defects in the pathogenesis of motor neuron disease and especially in components of the microtubule-based transport system. Here we will review our recent work aiming to elucidate the role of peripherin in amyotrophic lateral sclerosis (ALS) and to address the mechanism of disease caused by deletions in the ALS2 gene that cause recessive forms of juvenile ALS and primary lateral sclerosis (PLS). Peripherin is an intermediate filament protein detected in spheroids, a hallmark of ALS, and increased levels of peripherin mRNA have been found in some ALS cases. Our transgenic mouse and cell culture studies support the view of a peripherin involvement in ALS. However, a gene knockout approach demonstrated that peripherin is not a key contributor of motor neuron disease caused by mutant superoxide dismutase linked to familial ALS. A recent breakthrough in the field of ALS came with the discovery of frameshift deletions in the ALS2 gene coding for Alsin. Our transfection experiments in cultured cells suggest that Alsin is a cytoskeletal protein with dual endosomal and centrosomal localizations. We have generated a mouse knockout for Alsin that develops progressive motor dysfunction during ageing. Thus, it is anticipated that this mouse model will be useful to investigate the pathogenic pathways linked to Alsin gene mutations.

Amyotrophic Lateral Sclerosis↗
PubMed1994

The distribution of novel intermediate filament proteins defines subpopulations of myenteric neurons in rat intestine.

BACKGROUND/AIMS: Recent studies with neurofilament antibodies as neuronal markers have shown subpopulations of myenteric neurons that do not contain neurofilament proteins. Novel neuronal intermediate filament proteins alpha-internexin, peripherin, and nestin have been identified. The aim of this study was to examine the distribution of these novel intermediate filaments in comparison with neurofilaments in myenteric plexus neurons. METHODS: Using indirect immunofluorescence techniques in whole-mount cryostat sections from neonate and adult rat small intestine and in primary cultures of myenteric neurons, the distribution of neurofilaments, alpha-internexin, peripherin, and nestin was studied in comparison with the neuronal marker protein gene product (PGP) 9.5 in myenteric neurons. RESULTS: Sixty-five percent of neurons contained neurofilament triplet proteins. alpha-Internexin and/or peripherin were found in the neurofilament-negative neurons. PGP 9.5 was present in 80% of the myenteric neurons. Of the neurons that were PGP negative, > 95% contained peripherin or alpha-internexin. Nestin was not found in either neonate or adult myenteric neurons but was seen in glial cells in culture. CONCLUSIONS: The results suggest that a subpopulation of myenteric neurons lacks neurofilament triplet proteins but contains either peripherin, alpha-internexin, or both. This selective distribution of intermediate filaments in subpopulations of enteric neurons may support differential roles in these structurally unique neurons.

Animals↗
PubMed1988

[Melanotic adenocarcinoma of the uterus. Neuroendocrine tumor of the uterus].

The case reported concerns a 76-year-old woman under treatment for a previously diagnosed "poorly differentiated endocervical adenocarcinoma". New biopsies revealed an adenocarcinomatous tumor with unexpected melanotic pigmentation. The patient underwent cesium therapy followed by colpohysterectomy with lymphadenectomy. As there were no metastases, external complementary radiotherapy was not used. Four months after surgery, a large recurrence was detected; surgical excision proved impossible but revealed a grossly pigmented tumor from which several samples were taken. The patient died 11 months after the first consultation. No autopsy was performed. Morphological study was done on the initial biopsy, on the uterine tumor and on the recurrent tumor, using histological, cytological, ultrastructural and immunohistochemical techniques. Flow cytometry and biochemical study were also carried out on the recurrent tumor. All the samples studied histologically revealed uniform tumor morphology showing a poorly differentiated adenocarcinoma with an irregular distribution of melanin pigmentation (Fontana +). Electron microscopy confirmed the epithelial nature of the tumor, showing differentiated apical poles with villosities, linked by desmosomes. Basement membranes were irregularly present. Electron microscopy also demonstrated the melanotic nature of the pigmentation with melanosomes and premelanosomes. A few membrane-bound neurosecretory granules were seen. Immunohistochemistry showed that the tumor contains no S 100 protein and that no staining was obtained with monoclonal antibodies against malignant melanoma. Hormonal secretion and chromogranin were not detected. Tumor cells contained neither GFAP nor neurofilaments. Positive staining was obtained for neuron specific enolase and synaptophysin. Tumor cells contained three types of intermediate filament proteins = Vimentin, cytokeratins and peripherin (peripherin is an intermediate filament protein identified in 1984 by Portier, of the college of France, who very kindly supplied the antiserum and was good enough to do most of the biochemical study. Peripherin is considered to be characteristic of the peripheral nervous system. This case is the first example of demonstration of peripherin in a tumor). The biochemical study gave the following results: Cytosol assays for estrogen and progesterone receptors were negative. Vimentin, cytokeratins and peripherin were demonstrated by a study carried out in the Collège de France. No GFAP was found. A study of the metabolism of melanin derivatives showed high levels of urinary dopamine, serum and cytosol L. dopa.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed2003

Increased expression of multiple neurofilament mRNAs during regeneration of vertebrate central nervous system axons.

Characteristic changes in the expression of neuronal intermediate filaments (nIFs), an abundant cytoskeletal component of vertebrate axons, accompany successful axon regeneration. In mammalian regenerating PNS, expression of nIFs that are characteristic of mature neurons becomes suppressed throughout regeneration, whereas that of peripherin, which is abundant in developing axons, increases. Comparable changes are absent from mammalian injured CNS; but in goldfish and lamprey CNS, expression of several nIFs increases during axon regrowth. To obtain a broader view of the nIF response of successfully regenerating vertebrate CNS, in situ hybridization and video densitometry were used to track multiple nIF mRNAs during optic axon regeneration in Xenopus laevis. As in other successfully regenerating systems, peripherin expression increased rapidly after injury and expression of those nIFs characteristic of mature retinal ganglion cells decreased. Unlike the decrease in nIF mRNAs of regenerating PNS, that of Xenopus retinal ganglion cells was transient, with most nIF mRNAs increasing above normal during axon regrowth. At the peak of regeneration, increases in each nIF mRNA resulted in a doubling of the total amount of nIF mRNA, as well as a shift in the relative proportions contributed by each nIF. The relative proportions of peripherin and NF-M increased above normal, whereas proportions of xefiltin and NF-L decreased and that of XNIF remained the same. The increases in peripherin and NF-M mRNAs were accompanied by increases in protein. These results are consistent with the hypothesis that successful axon regeneration involves changes in nIF subunit composition conducive to growth and argue that a successful injury response differs between CNS and PNS.

Animals↗
PubMed2002

Expression of intermediate filaments in conjunctival melanocytic lesions.

BACKGROUND: To our knowledge there have been no studies on intermediate filament (IF) expression in conjunctival melanocytic tumors to date. Melanocytic lesions occurring at various body sites are known to express, in addition to the predominant IF protein vimentin, the epithelial-specific cytokeratins (CKs) and the neuronal IF peripherin. The present study was therefore carried out to assess the expression of IF proteins in conjunctival melanocytic lesions. METHODS: Paraffin-embedded material from 34 tumors - 16 conjunctival nevi, nine specimens of primary acquired melanosis (PAM; eight with and one without atypia), and nine conjunctival melanomas - was assessed after the application of a panel of antibodies directed against diverse IF proteins, including vimentin, CKs and peripherin. RESULTS: The most significant finding of this study was that all the tumors investigated expressed vimentin exclusively. While simple-epithelium CKs were found in epithelial cysts of nevi and in pseudoglandular portions adjacent to the melanoma, they were not identified in the tumor cells themselves. Similarly, peripherin and neurofilaments were not detected within any of the tumor cells. CONCLUSION: The IF expression pattern of conjunctival melanocytic lesions differs from that seen in melanocytic tumors of other body sites (including uveal melanomas), in that it includes neither CKs nor peripherin.

Conjunctiva↗
PubMed1992

Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies.

The molecules essential to the continual morphogenesis and shedding of the opsin-containing disks of vertebrate photoreceptors are largely unknown. We describe a 37 kd protein, rom-1, which is 35% identical and structurally similar to peripherin/retinal degeneration slow (rds). Like peripherin, rom-1 is a retina-specific integral membrane protein localized to the photoreceptor disk rim. The two proteins are similarly oriented in the membrane, and each has a highly conserved (15/16 residues) cysteine- and proline-rich domain in the disk lumen. Although both rom-1 and peripherin form disulfide-linked dimers, they do not form heterodimers with each other, but appear to associate noncovalently. These results suggest both that rom-1 and peripherin are functionally related members of a new photoreceptor-specific protein family and that rom-1, like peripherin, is likely to be important to outer segment morphogenesis. The association of mutations in RDS with retinitis pigmentosa indicates that ROM1 is a strong candidate gene for human retinopathies.

Adult↗
PubMed2000

Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis.

The homologous membrane proteins Rom-1 and peripherin-2 are localized to the disk rims of photoreceptor outer segments (OSs), where they associate as tetramers and larger oligomers. Disk rims are thought to be critical for disk morphogenesis, OS renewal and the maintenance of OS structure, but the molecules which regulate these processes are unknown. Although peripherin-2 is known to be required for OS formation (because Prph2-/- mice do not form OSs; ref. 6), and mutations in RDS (the human homologue of Prph2) cause retinal degeneration, the relationship of Rom-1 to these processes is uncertain. Here we show that Rom1-/- mice form OSs in which peripherin-2 homotetramers are localized to the disk rims, indicating that peripherin-2 alone is sufficient for both disk and OS morphogenesis. The disks produced in Rom1-/- mice were large, rod OSs were highly disorganized (a phenotype which largely normalized with age) and rod photoreceptors died slowly by apoptosis. Furthermore, the maximal photoresponse of Rom1-/- rod photoreceptors was lower than that of controls. We conclude that Rom-1 is required for the regulation of disk morphogenesis and the viability of mammalian rod photoreceptors, and that mutations in human ROM1 may cause recessive photoreceptor degeneration.

Animals↗
PubMed2005

Timing of neuronal intermediate filament proteins expression in the mouse vomeronasal organ during pre- and postnatal development. An immunohistochemical study.

Several types of intermediate filament proteins are expressed in developing and mature neurons; they cooperate with other cytoskeletal components to sustain neuronal function from early neurogenesis onward. In this work the timing of expression of nestin, peripherin, internexin, and the neuronal intermediate filament triplet [polypeptide subunits of low (NF-L), medium (NF-M), and high (NF-H) molecular weight] was investigated in the developing fetal and postnatal mouse vomeronasal organ (VNO) by means of immunohistochemistry. The results show that the sequence of expression of intermediate filament proteins is internexin, nestin, and NF-M in the developing vomeronasal sensory epithelium; internexin, peripherin, and NF-M in the developing vomeronasal nerve; and nestin, internexin and peripherin, NF-L, and NF-M in the nerve supply to accessory structures of the VNO. At sexual maturity (2 months) NF-M is only expressed in vomeronasal neurons and NF-M, NF-L and peripherin are expressed in extrinsic nerves supplying VNO structures. The differential distribution of intermediate filament proteins in the vomeronasal sensory epithelium and nerve is discussed in terms of the cell types present therein. It is concluded that several intermediate filament proteins are sequentially expressed during intrauterine development of the VNO neural structures in a different pattern according to the different components of the VNO.

Animals↗
PubMed1993

Cloning of the human and murine ROM1 genes: genomic organization and sequence conservation.

Rom-1 and peripherin are related membrane proteins of the photoreceptor outer segments. Both proteins are located at the rims of the photoreceptor disks, where they may act jointly in disk biogenesis. Mutations in the gene (RDS) encoding peripherin cause autosomal dominant retinitis pigmentosa, autosomal dominant punctata albescens and butterfly macular degeneration in man, and retinal degeneration slow in mice. To facilitate ROM1 mutation and linkage analysis in inherited retinal diseases, we cloned and characterized the human and murine ROM1 genes. In both species, the ROM1 coding region is contained within approximately 1.8 kb of genomic DNA and is interrupted by only two introns. The structures of the ROM1 and RDS genes are similar, with perfect conservation of the intron splice sites. Putative transcription regulatory regions of the ROM1 locus, 5' to an apparent transcription start site, were identified by cloning the mouse Rom-1 gene and comparing the sequence to the human homologue. Alignment of the human and murine rom-1 predicted protein sequences with the peripherin polypeptides of four species reveals a high degree of conservation (47% overall identity between the six proteins) in the central hydrophilic domain of the two family members. Despite this conservation of sequence, the predicted pI's of only this region of rom-1 and peripherin differ substantially, being 5.2 and 8.2, respectively. The charge difference in this region may mediate the non-covalent association of these two proteins in vivo. The conserved genomic structure and sequence of ROM1 and RDS indicates that these genes evolved from a common ancestor by duplication event.

Amino Acid Sequence↗
PubMed2000

The spatial and temporal expression of outer segment proteins during development of Macaca monkey cones.

PURPOSE: To characterize the spatial and temporal expression of key structural and phototransduction cascade proteins in the monkey cone outer segment (OS). METHODS: Retinas from Macaca monkeys from ages fetal day (Fd) 89 through adulthood were double labeled using immunofluorescence for short (S) or long/medium (L/M) wavelength-sensitive cone opsin and either a structural protein (peripherin) or a phototransduction cascade protein (alpha-transducin [alpha-T], phosphodiesterase [PDE], or rhodopsin kinase [RK]). The spatial and temporal patterns of expression for each protein at each age were determined and graphed as a percentage of retinal coverage. RESULTS: In both cone types, opsins and phototransduction proteins appear first in the fovea and last at the retinal edge. Peripherin appears concomitantly with opsin in both S and L/M cones, but S cones express peripherin and opsin 1 to 3 weeks before neighboring L/M cones. Alpha-T, PDE, and RK are expressed together in the L/M cone OS shortly after L/M opsin appears. Phototransduction proteins are not expressed in S cones until 1 to 3 weeks after the appearance of S opsin and at the same time that neighboring cones are expressing both L/M opsin and phototransduction proteins. CONCLUSIONS: The concomitant appearance of opsin and peripherin strongly suggests roles in promoting the structural integrity of the developing OS. Phototransduction cascade proteins appear in the developing OS at the same time as one another, but after opsin. The significant lag between their expression and that of S cone opsin indicates that phototransduction proteins are not essential for OS formation, nor does opsin expression trigger their expression. The different temporal but similar spatial expression patterns of phototransduction proteins within S and L/M cones suggests that some local signal(s) coordinates their appearance.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

An intact intermediate filament network is required for collateral sprouting of small diameter nerve fibers.

Expression of the intermediate filament (IF) protein peripherin is initiated during development at the time of axonal extension and increases during regeneration of nerve fibers. To test whether the IF network is essential for neuron process outgrowth in the mature organism in vivo, we disrupted endogenous peripherin IF in small-sized dorsal root ganglion (DRG) neurons in transgenic mice via expression of a mutant peripherin transgene under control of peripherin gene regulatory sequences. Anatomical and functional analyses showed that these neurons send peripheral and central axonal projections to correct targets, express correct neuropeptides, and mediate acute pain responses normally. However, disruption of IF significantly impaired the ability of uninjured small-sized DRG neurons to sprout collateral axons into adjacent denervated skin, indicating a critical role for intact IF in plasticity, specifically in compensatory nociceptive nerve sprouting.

Animals↗