Hair follicle development is initiated by reciprocal molecular interactions between the placode-forming epithelium and the underlying mesenchyme. Cell fate transformation in dermal fibroblasts generates a cell niche for placode induction by activation of signaling pathways WNT, EDA, and FGF in the epithelium. These successive paracrine epithelial signals initiate dermal condensation in the underlying mesenchyme. Although epithelial signaling from the placode to mesenchyme is better described, little is known about primary mesenchymal signals resulting in placode induction. Using genetic approach in mice, we show that Meis2 expression in cells derived from the neural crest is critical for whisker formation and also for branching of trigeminal nerves. While whisker formation is independent of the trigeminal sensory innervation, MEIS2 in mesenchymal dermal cells orchestrates the initial steps of epithelial placode formation and subsequent dermal condensation. MEIS2 regulates the expression of transcription factor Foxd1, which is typical of pre-dermal condensation. However, deletion of Foxd1 does not affect whisker development. Overall, our data suggest an early role of mesenchymal MEIS2 during whisker formation and provide evidence that whiskers can normally develop in the absence of sensory innervation or Foxd1 expression.
- MeSH
- crista neuralis MeSH
- forkhead transkripční faktory metabolismus genetika MeSH
- homeodoménové proteiny * metabolismus genetika MeSH
- mezoderm * metabolismus MeSH
- myši MeSH
- nervus trigeminus * MeSH
- vibrissae * inervace růst a vývoj embryologie MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Donor nerve selection is a crucial factor in determining clinical outcomes of facial reanimation. Although dual innervation approaches using two neurotizers have shown promise, there is a lack of evidence-based comparison in the literature. Furthermore, no animal model of dual reinnervation has yet been published. This study aimed to establish such a model and verify its technical and anatomical feasibility by performing dual-innervated reanimation approaches in Wistar rats. METHODS: Fifteen Wistar rats were divided into four experimental groups and one control group. The sural nerve was exposed and used as a cross-face nerve graft (CFNG), which was then anastomosed to the contralateral buccal branch of the facial nerve through a subcutaneous tunnel on the forehead. The CFNG, the masseteric nerve (MN), and the recipient nerve were coapted in one or two stages. The length and width of the utilized structures were measured under an operating microscope. Return of whisker motion was visually confirmed. RESULTS: Nine out of the eleven rats that underwent surgery survived the procedure. Whisker motion was observed in all experimental animals, indicating successful reinnervation. The mean duration of the surgical procedures did not differ significantly between the experimental groups, ensuring similar conditions for all groups. CONCLUSIONS: Our experimental study confirmed that the proposed reanimation model in Wistar rats is anatomically and technically feasible, with a high success rate, and shows good prospects for future experiments.
- MeSH
- faciální paralýza * chirurgie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- nervus facialis * chirurgie fyziologie MeSH
- nervus suralis chirurgie MeSH
- potkani Wistar MeSH
- regenerace nervu * fyziologie MeSH
- vibrissae fyziologie inervace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Central sensitization is a key mechanism in the pathology of several neuropathic pain disorders. We aimed to investigate the underlying brain connectivity changes in a rat model of chronic pain. Non-noxious whisker stimulation was used to evoke blood-oxygen-level-dependent (BOLD) responses in a block-design functional Magnetic Resonance Imaging (fMRI) experiment on 9.4T. Measurements were repeated two days and one week after injecting complete Freund's adjuvant into the rats' whisker pad. We found that acute pain reduced activation in the barrel cortex, most probably due to a plateau effect. After one week, increased activation of the anterior cingulate cortex was found. Analyses of effective connectivity driven by stimulus-related activation revealed that chronic pain-related central sensitization manifested as a widespread alteration in the activity of the somatosensory network. Changes were mainly mediated by the anterior cingulate cortex and the striatum and affected the somatosensory and motor cortices and the superior colliculus. Functional connectivity analysis of nested BOLD oscillations justified that the anterior cingular-somatosensory interplay is a key element of network changes. Additionally, a decreased cingulo-motor functional connectivity implies that alterations also involve the output tract of the network. Our results extend the knowledge about the role of the cingulate cortex in the chronification of pain and indicate that integration of multiple connectivity analysis could be fruitful in studying the central sensitization in the pain matrix.
- MeSH
- chronická bolest diagnostické zobrazování patofyziologie MeSH
- cingulární gyrus diagnostické zobrazování patofyziologie MeSH
- ganglion trigeminale patofyziologie MeSH
- kyslík krev MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku MeSH
- modely nemocí na zvířatech MeSH
- mozkový krevní oběh fyziologie MeSH
- nervové dráhy diagnostické zobrazování patofyziologie MeSH
- nervus trigeminus patofyziologie MeSH
- potkani Sprague-Dawley MeSH
- senzibilizace centrálního nervového systému fyziologie MeSH
- vibrissae fyziologie MeSH
- zánět diagnostické zobrazování patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Sensory deprivation in one modality can enhance the development of the remaining modalities via mechanisms of synaptic plasticity. Mice of the C3H strain suffer from RD1 retinal degeneration that leads to visual impairment at weaning age. We examined a role of whiskers in compensation of the visual deficit. In order to differentiate the contribution of the whiskers from other mechanisms that can take part in the compensation, we investigated the effect of both chronic and acute tactile deprivation. Three-month-old mice were used. We examined motor skills (rotarod, beam walking test), gait control (CatWalk system), spontaneous motor activity (open field) and CNS excitability to an acoustic stimulus for assessment of compensatory changes in auditory system (audiogenic epilepsy). In the sighted mice, the only effect was a decline in their rotarod test performance after acute whisker removal. In the blind animals, chronic tactile deprivation caused changes in their gait and impaired the performance in motor tests. Some other compensatory mechanisms were involved but the whiskers are essential for the compensation as it emerged from more marked change of gait and the worsening of the motor performance after the acute whisker removal. Both chronic and acute tactile deprivation induced anxiety-like behaviour. Only a combination of blindness and chronic tactile deprivation led to an increased sense of hearing.
- MeSH
- akustická stimulace MeSH
- chůze (způsob) MeSH
- degenerace retiny patofyziologie psychologie MeSH
- motorické dovednosti MeSH
- myši inbrední C3H MeSH
- pohybová aktivita MeSH
- senzorická deprivace MeSH
- slepota patofyziologie psychologie MeSH
- sluch fyziologie MeSH
- sluchová percepce * MeSH
- úzkost patofyziologie psychologie MeSH
- vibrissae fyziologie MeSH
- zraková percepce * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Neural crest (NC) is a transient embryonic tissue, whose cells are motile and multipotent until they reach their destination and differentiate according to microenvironmental cues into a variety of cell types. However, a subpopulation of these cells remains multipotent. They were found, among other locations, in a bulge of adult murine whisker follicle and were designated epidermal neural crest stem cells (EPI-NCSCs). The aim of this work is to ascertain whether the EPI-NCSCs could be isolated from human hair follicles as well. Due to their exceptional properties, they could represent potential candidates for stem cell therapy. The presented work focuses on the isolation and characterization of EPI-NCSCs from human skin. We obtained a population of cells that expressed markers of NC, NC progeny and general stem cell markers. After prolonged cultivation, the subpopulation of cells spontaneously differentiated into some of NC derivatives, i.e. neurons, smooth muscle cells and Schwann cell progenitors. Targeted differentiation with neuregulin 1 highly increased the number of Schwann cells in the culture. Human EPI-NCSCs could also grow under non-adherent conditions and form 3-dimensional spheres. Microarray analysis was performed and gene profile of human EPI-NCSCs was compared with the list of key genes of murine EPI-NCSCs and the list of genes up-regulated in newly induced NC cells. This revealed 94% and 88% similarity, respectively. All presented results strongly support the NCSC identity and multipotency of isolated human cells. These cells could thus be used in regenerative medicine, especially because of the easy accessibility of donor tissue.
- MeSH
- buněčná diferenciace MeSH
- crista neuralis cytologie metabolismus MeSH
- financování organizované MeSH
- imunohistochemie MeSH
- kmenové buňky cytologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- multipotentní kmenové buňky cytologie metabolismus MeSH
- myši MeSH
- neurony MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- Schwannovy buňky MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- stanovení celkové genové exprese MeSH
- transplantace kmenových buněk MeSH
- vibrissae MeSH
- vlasový folikul cytologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
