A common question in organ regeneration is the extent to which regeneration recapitulates embryonic development. To investigate this concept, we compared the expression of two highly interlinked and ...essential genes for salivary gland development, Sox9 and Fgf10, during submandibular gland development, homeostasis and regeneration. Salivary gland duct ligation/deligation model was used as a regenerative model. Fgf10 and Sox9 expression changed during regeneration compared to homeostasis, suggesting that these key developmental genes play important roles during regeneration, however, significantly both displayed different patterns of expression in the regenerating gland compared to the developing gland. Regenerating glands, which during homeostasis had very few weakly expressing Sox9‐positive cells in the striated/granular ducts, displayed elevated expression of Sox9 within these ducts. This pattern is in contrast to embryonic development, where Sox9 expression was absent in the proximally developing ducts. However, similar to the elevated expression at the distal tip of the epithelium in developing salivary glands, regenerating glands displayed elevated expression in a subpopulation of acinar cells, which during homeostasis expressed Sox9 at lower levels. A shift in expression of Fgf10 was observed from a widespread mesenchymal pattern during organogenesis to a more limited and predominantly epithelial pattern during homeostasis in the adult. This restricted expression in epithelial cells was maintained during regeneration, with no clear upregulation in the surrounding mesenchyme, as might be expected if regeneration recapitulated development. As both Fgf10 and Sox9 were upregulated in proximal ducts during regeneration, this suggests that the positive regulation of Sox9 by Fgf10, essential during development, is partially reawakened during regeneration using this model. Together these data suggest that developmentally important genes play a key role in salivary gland regeneration but do not precisely mimic the roles observed during development.
A common question in organ regeneration is the extent to which regeneration recapitulates embryonic development. To investigate this concept, we compared the expression of two highly interlinked and essential genes for salivary gland development, Sox9 and Fgf10, during submandibular gland development, homeostasis and regeneration. Our data suggest that developmentally important genes play a key role in salivary gland regeneration but do not precisely mimic the roles observed during development.
Aquaporins (AQPs) are essential to coordinate the transit of water and ions through the cell membrane. In salivary glands (SGs), AQPs have been associated with saliva formation, facilitating water ...absorption through the epithelium during the formation of hypotonic saliva, which is then secreted into the oral cavity. Different members of the AQP family have been suggested to play distinct roles during embryonic development, highlighted by their specific expression patterns. Here, we have investigated the expression patterns of AQP‐1, AQP‐3 and AQP‐5 by immunofluorescence at key stages of salivary gland development, utilising cultured mouse embryonic submandibular (SMG) and sublingual (SLG) glands. The expression of AQPs was compared to a mitotic marker, phospho‐histone 3 (PH3), a myoepithelial marker, smooth muscle actin (SMA), and a vascular marker, CD31. Qualitative analysis revealed that AQP‐1 and AQP‐3 were primarily expressed during the earlier phases of SG morphogenesis and were associated with cells undergoing mitotic processes (PH3‐positive). AQP‐5, in contrast, was not associated to mitotic figures, but was predominantly expressed during late stages of SG morphogenesis. Our results highlight that AQPs are expressed from early stages of SG morphogenesis and exhibit complimentary expression patterns that may contribute to the morphogenesis of salivary glands.
AQP‐1 in mouse developing salivary glandsA: AQP‐1 expression in basal cell membranes (green ‐ A’) co‐expressed with PH3 nuclear staining (red ‐ A’’). B: At E14.5: AQP‐1 and PH3, showing expression in the ductal and acinar epithelium. C and D: Salivary gland at E16.5, showing condensed mitotic nuclei (blue) colocalised with AQP‐1 in several acinar cells and ductal epithelia.
is necessary for the development of a number of organs that fail to develop or are reduced in size in the null mutant. Here we have knocked out
specifically in the neural crest driven by
. The
mouse ...phenocopies many of the null mutant defects, including cleft palate, loss of salivary glands, and ocular glands, highlighting the neural crest origin of the
expressing mesenchyme surrounding these organs. In contrast tissues such as the limbs and lungs, where
is expressed by the surrounding mesoderm, were unaffected, as was the pituitary gland where
is expressed by the neuroepithelium. The circumvallate papilla of the tongue formed but was hypoplastic in the conditional and
null embryos, suggesting that other sources of FGF can compensate in development of this structure. The tracheal cartilage rings showed normal patterning in the conditional knockout, indicating that the source of
for this tissue is mesodermal, which was confirmed using
to lineage trace the boundary of the neural crest in this region. The thyroid, thymus, and parathyroid glands surrounding the trachea were present but hypoplastic in the conditional mutant, indicating that a neighboring source of mesodermal
might be able to partially compensate for loss of neural crest derived
.
The vestibular lamina (VL) is a transient developmental structure that forms the lip furrow, creating a gap between the lips/cheeks and teeth (oral vestibule). Surprisingly, little is known about the ...development of the VL and its relationship to the adjacent dental lamina (DL), which forms the teeth. In some congenital disorders, such as Ellis-van Creveld (EVC) syndrome, development of the VL is disrupted and multiple supernumerary frenula form, physically linking the lips and teeth. Here, we assess the normal development of the VL in human embryos from 6.5 (CS19) to 13 weeks of development, showing the close relationship between the VL and DL, from initiation to differentiation. In the anterior lower region, the two structures arise from the same epithelial thickening. The VL then undergoes complex morphogenetic changes during development, forming a branched structure that separates to create the vestibule. Changing expression of keratins highlight the differentiation patterns in the VL, with fissure formation linked to the onset of filaggrin. Apoptosis is involved in removal of the central portion of the VL to create a broad furrow between the future cheek and gum. This research forms an essential base to further explore developmental defects in this part of the oral cavity.
Abstract
A small-momentum-width muon beam, so-called ultra-slow muon beam, can be generated by laser ionization of muonium. To realize efficient ultra-slow muon generation, the Lyman-alpha and below ...360 nm coherent light are required to resonantly excite the muonium from the ground state to 2
p
and sequentially ionizes excited muonium to the unbound state. At the J-PARC MLF Ultra-Slow Muon beamline, we have successfully generated Lyman-alpha coherent light exceeding 10 μJ using an all-solid-state laser and high-efficiency vacuum ultraviolet light generation technologies. In this paper, we will describe the intense Lyman-alpha light source.
Present status of J-PARC MUSE Shimomura, K; Koda, A; Pant, A D ...
Journal of physics. Conference series,
03/2023, Letnik:
2462, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
At J-PARC MUSE, since the
µ
SR2017 conference and up to FY2022, there have been several new developments at the facility, including the completion of a new experimental area S2 at the ...surface muon beamline S-line and the first muon beam extraction to the H1 area in the H-line, mainly to carry out high-statistics fundamental physics experiments. Several new studies are also underway, such as applying negative muon non-destructive elemental analysis to the analysis of samples returned from the asteroid Ryugu in the D2 area of the D-line. This paper reports on the latest status of MUSE.
Little is known about the key molecules that regulate cell division during organogenesis. Here we determine the role of the cell cycle promoter aurora kinase B (AURKB) during development, using ...embryonic salivary glands (E-SGs) as a model. AURKB is a serine/threonine kinase that regulates key events in mitosis, which makes it an attractive target for tailored anticancer therapy. Many reports have elaborated on the role of AURKB in neoplasia and cancer; however, no previous study has shown its role during organ development. Our previous experiments have highlighted the essential requirement for AURKB during adult exocrine regeneration. To investigate if AURKB is similarly required for progression during embryonic development, we pharmacologically inhibited AURKB in developing submandibular glands (SMGs) at embryonic day (E)13.5 and E16.5, using the highly potent and selective drug Barasertib. Inhibition of AURKB interfered with the expansion of the embryonic buds. Interestingly, this effect on SMG development was also seen when the mature explants (E16.5) were incubated for 24 h with another cell cycle inhibitor Aphidicolin. Barasertib prompted apoptosis, DNA damage and senescence, the markers of which (cleaved caspase 3, γH2AX, SA-βgal and p21, respectively), were predominantly seen in the developing buds. In addition to a reduction in cell cycling and proliferation of the epithelial cells in response to AURKB inhibition, Barasertib treatment led to an excessive generation of reactive oxygen species (ROS) that resulted in downregulation of the acinar differentiation marker Mist1. Importantly, inhibition of ROS was able to rescue this loss of identity, with Mist1 expression maintained despite loss of AURKB. Together, these data identify AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis.
Abstract
The Super-Omega beamline at J-PARC Materials and Life Science Experimental Facility provides an intense pulsed slow positive muon beam. Combined with a muonium production target and laser ...light for muonium ionization, the pulsed ultra-slow muon facility has been developed. At the facility, a spectrometer for muon spin rotation measurements using ultra-slow muons is under commissioning. In this paper, we will report on the current status of the beam optics optimization of slow muon transport and ultra-slow muon extraction to improve the intensity and quality of the ultra-slow muon beam.
Abstract
At J-PARC MLF, MUSE provides the world-highest flux of pulsed muon beams. U-Line, one of the four beamlines in the facility, features an intense surface muon beam from Super-Omega and ...Ultra-slow muon generated by laser ionization of thermal muonium in vacuo. The Ultra-slow muon beam is characterized by variable energy from sub-keV to tens of keV and a time resolution of several tens of times better than that of ordinary pulsed beams. These features enable the study of interesting phenomena localized at surfaces and near interfaces and fast dynamics that cannot be observed with ordinary pulsed beams. Commissioning of the beamline and instruments is underway in preparation for the start of user programs. This paper presents an overview of the facility, its current status, and its prospects.
Abstract
At J-PARC, the MuSEUM (Muonium Spectroscopy Experiment Using Microwave) collaboration aims to precisely measure the ground-state hyperfine splitting of muonium atoms arising from the muon ...and electron spins. The pulsed muon beam is stopped in a krypton gas cell to form muonium atoms. The transitions of spin states are induced with a microwave cavity, which are then measured by positron counters. After the previously performed successful measurements with a nearly-zero magnetic field, we are currently planning a measurement with the 2.9T magnetic field by measuring two Zeeman-split sub-levels, so that increased statistics will allow us to more precisely determine the transition frequency down to ∼1ppb. Moreover, a new microwave cavity with a unique geometry is being designed to perform the measurement at an even stronger field of 2.9T in the future.
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