Mesenchymal control over elongating and branching morphogenesis in salivary gland development

Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 209-221
Author(s):  
Hiroyuki Nogawa ◽  
Takeo Mizuno

Recombination of the epithelium and mesenchyme between quail anterior submaxillary gland (elongating type) and quail anterior lingual or mouse submaxillary gland (branching type) was effected in vitro to clarify whether the elongating morphogenesis was directed by the epithelial or the mesenchymal component. Quail anterior submaxillary epithelium recombined with quail anterior lingual or mouse submaxillary mesenchyme came to branch. Conversely, quail anterior lingual or 12-day mouse submaxillary epithelium recombined with quail anterior submaxillary mesenchyme came to elongate, though the mesenchyme was less effective with 13-day mouse submaxillary epithelium. These results suggest that the elongating or branching morphogenesis of quail salivary glands is controlled by the mesenchyme.

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kenji Okumura ◽  
Masanori Shinohara ◽  
Fumio Endo

Branching morphogenesis (BrM), an essential step for salivary gland development, requires epithelial-mesenchymal interactions. BrM is impaired when the surrounding mesenchyme is detached from the salivary epithelium during the pseudoglandular stage. It is believed that the salivary mesenchyme is indispensable for BrM, however, an extracellular matrix gel with exogenous EGF can be used as a substitute for the mesenchyme during BrM in the developing salivary epithelium. Stem/progenitor cells isolated from salivary glands in humans and rodents can be classified as mesenchymal stem cell-like, bone-marrow-derived, duct cell-like, and embryonic epithelium-like cells. Salivary-gland-derived progenitor (SGP) cells isolated from duct-ligated rats, mice, and swine submandibular glands share similar characteristics, including intracellular laminin andα6β1-integrin expression, similar to the embryonic salivary epithelia during the pseudoglandular stage. Progenitor cells also isolated from human salivary glands (human SGP cells) having the same characteristics differentiate into hepatocyte-like cells when transplanted into the liver. Similar to the dissociated embryonic salivary epithelium, human SGP cells aggregate to self-organize into branching organ-like structures on Matrigel plus exogenous EGF. These results suggest the possibility that tissue stem cells organize rudiment-like structures, and the embryonic cells that organize into whole tissues during development are preserved even in adult tissues.


1963 ◽  
Vol 205 (5) ◽  
pp. 1058-1062 ◽  
Author(s):  
L. H. Schneyer ◽  
C. A. Schneyer

Effects of pilocarpine on net movements of water and electrolytes in gland cells were investigated in vitro, using slices from submaxillary gland of rat. Slices were depleted of K, and loaded with Na, Cl, and water, by incubation in Krebs-Ringer phosphate with nitrogen atmosphere. After this, the slices were transferred to Krebs-Ringer phosphate with oxygen atmosphere. During this period with O2, pilocarpine caused apparent loss of water from cells, since tissue total water decreased and inulin space remained almost unchanged. Without pilocarpine during this time, water in cells increased. Electrolyte movements were also affected by pilocarpine. Specifically, there occurred reduction in net accumulation of K in total tissue and cells. Reduction in net extrusion of Na was suggested. Since, in vivo, an early effect of stimulation involves depletion of gland K, it appears that the current observations have relevance to normal secretion to the extent, at least, that in both circumstances stimulating agents reduce the ability of the cells to maintain stores of K.


2019 ◽  
Vol 98 (10) ◽  
pp. 1122-1130 ◽  
Author(s):  
T.H.N. Teshima ◽  
A.S. Tucker ◽  
S.V. Lourenço

Neuronal signaling is known to be required for salivary gland development, with parasympathetic nerves interacting with the surrounding tissues from early stages to maintain a progenitor cell population and control morphogenesis. In contrast, postganglionic sympathetic nerves arrive late in salivary gland development to perform a secretory function; however, no previous report has shown their role during development. Here, we show that a subset of neuronal cells within the parasympathetic submandibular ganglion (PSG) express the catecholaminergic marker tyrosine hydroxylase (TH) in developing murine and human submandibular glands. This sympathetic phenotype coincided with the expression of transcription factor Hand2 within the PSG from the bud stage (E12.5) of mouse embryonic salivary gland development. Hand2 was previously associated with the decision of neural crest cells to become sympathetic in other systems, suggesting a role in controlling neuronal fate in the salivary gland. The PSG therefore provides a population of TH-expressing neurons prior to the arrival of the postganglionic sympathetic axons from the superior cervical ganglion at E15.5. In culture, in the absence of nerves from the superior cervical ganglion, these PSG-derived TH neurons were clearly evident forming a network around the gland. Chemical ablation of dopamine receptors in explant culture with the neurotoxin 6-hydroxydopamine at early stages of gland development resulted in specific loss of the TH-positive neurons from the PSG, and subsequent branching was inhibited. Taken altogether, these results highlight for the first time the detailed developmental time course of TH-expressing neurons during murine salivary gland development and suggest a role for these neurons in branching morphogenesis.


2004 ◽  
Vol 72 (6) ◽  
pp. 3604-3608 ◽  
Author(s):  
Peter Preiser ◽  
Laurent Rénia ◽  
Naresh Singh ◽  
Bharath Balu ◽  
William Jarra ◽  
...  

ABSTRACT MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites.


1976 ◽  
Vol 64 (3) ◽  
pp. 727-742
Author(s):  
W. Kaufman

1. Salivary glands of the female ixodid tick, Dermacentor andersoni, secrete fluid in vitro when bathed in a slightly modified version of the mammalian tissue culture medium ‘TC 199′. 2. Rate of salivation in vitro increases with progression of feeding, but there is no comparable increase in dry weight of the salivary glands during the early phase of engorgement. Engorged ticks secreted at only 25% the rate of 90–250 mg ticks, indicating that salivary gland degeneration has already begun in the very early post-engorgement stage. 3. A salivary gland stimulating factor can be detected in the nervous system but not in other tissues. 4. Male salivary glands secrete at only 1/20th the rate of female glands. Thus males probably do not use their salivary glands as osmoregulatory organs. 5. From the uniform lack of response to ACh and uniform response to DA in 7 ixodid tick species, it is suggested that the control of salivation is similar throughout the ixodid family.


2019 ◽  
Vol 12 (1) ◽  
pp. 18 ◽  
Author(s):  
Roswitha Tönnesmann ◽  
Philipp Meyer ◽  
Matthias Eder ◽  
Ann-Christin Baranski

Irradiation of salivary glands remains the main dose-limiting side effect of therapeutic PSMA-inhibitors, especially when using alpha emitters. Thus, further advances in radiopharmaceutical design and therapy strategies are needed to reduce salivary gland uptake, thereby allowing the administration of higher doses and potentially resulting in improved response rates and better tumor control. As the uptake mechanism remains unknown, this work investigates the salivary gland uptake of [177Lu]Lu-PSMA-617 by autoradiography studies on pig salivary gland tissue and on PSMA-overexpressing LNCaP cell membrane pellets. Displacement studies were performed with non-labeled PSMA-617 and 2-PMPA, respectively. The uptake of [177Lu]Lu-PSMA-617 in glandular areas was determined to be partly PSMA-specific, with a high non-specific uptake fraction. The study emphasizes that [177Lu]Lu-PSMA-617 accumulation in pig salivary glands can be attributed to a combination of both specific and non-specific uptake mechanisms. The observation is of high impact for future design of novel radiopharmaceuticals addressing the dose-limiting salivary gland irradiation of current alpha endoradiotherapy in prostate cancer.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
S. Hall-Mendelin ◽  
P. O'Donoghue ◽  
R. B. Atwell ◽  
R. Lee ◽  
R. A. Hall

TheIxodes holocyclustick causes paralysis in up to 10,000 companion and domestic animals each year in Australia. Treatment requires the removal of the parasite and the administration of a commercial tick antiserum that is prepared from hyperimmune dogs. Each batch of this serum is initially tested for toxin-neutralising potency in a mouse bioassay that is expensive, time consuming, and subjective. With the aim of developing a rapidin vitroassay to replace the bioassay, we used a partially purified antigen prepared fromI. holocyclussalivary glands to develop an ELISA to detect toxin-reactive antibodies in hyperimmune dog sera. The optimised ELISA reliably detected antibodies reactive toI. holocyclussalivary gland antigens. Parallel testing of sera with a negative control antigen prepared from the salivary glands of the nontoxic tickRhipicephalus(Boophilus)microplusprovided further evidence that we were detecting toxin-specific antibodies in the assay. Using the ELISA, we could also detect antibodies induced in rats after experimental infestation withI. holocyclus. This assay shows promise as an alternative means of assessing the potency of batches of hyperimmune dog serum and to screen for toxin-reactive monoclonal antibodies produced from immunised rodents.


Development ◽  
1983 ◽  
Vol 73 (1) ◽  
pp. 221-232
Author(s):  
Hiroyuki Nogawa

Mouse submaxillary epithelium undergoes branching morphogenesis with increase in the curvature of its surface in vivo. Recombination experiments in vitro of the epithelium and mesenchyme between 13- and 14-day rudiments showed (1) that the 14-day mesenchyme more actively induced the epithelium to branch than the 13-day mesenchyme, (2) that the 14-day mesenchyme could produce clefts on smaller epithelial lobes than the 13-day mesenchyme, (3) that the 14-day mesenchyme produced lobes with similar diameter to lobes of the 14-day intact rudiment, and (4) that the lobular morphology of assembled 14-day lobes became obscure in recombinates with the 13-day mesenchyme while it was well maintained in recombinates with the 14-day mesenchyme. From these results it is concluded that the mesenchyme determines the curvature of epithelial surface, and that clefts are formed on the epithelial surface as a result of increase in the epithelial curvature.


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