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Functional Differentiation of Salivary Glands

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Abstract

The sections in this article are:

1 Morphogenesis
1.1 Descriptive Embryology
1.2 Developmental Regulation
2 Cytodifferentiation
2.1 Descriptive Embryology
2.2 Developmental Regulation
3 Stimulus‐Secretion Coupling Systems
3.1 Cyclic Adenosine 5’ ‐Monophosphate‐Generating System
3.2 Cell Surface Receptors
3.3 Physiological Coupling With Nerves
4 Summary
Figure 1. Figure 1.

Diagram of major stages in development of salivary glands. Stage I: salivary epithelium begins to grow down from oral epithelium into underlying mesenchyme (MES). Epithelium is separated from mesenchyme by intact basal lamina (BL). Stage II: epithelium continues to proliferate and grow. Mesenchyme condenses to form a discrete capsule. Collagen type I is deposited in proximity to epithelial basal lamina. Stages IIIa and IIIb: specific morphogenetic branching pattern is established through differential cell division at growing ends of branch buds and through changes in synthesis and degradation of basal lamina. Collagen type I stabilizes lamina in clefts but lamina becomes discontinuous at growing ends. Direct epithelial‐mesenchymal interactions occur at growing ends of early branches. Stage IV: branching continues. Cells become polarized and amplify secretory protein synthesis. Stage V: cells initiate packaging of secretory proteins into zymogen granules. Myoepithelial cells (MEC) differentiate at periphery of developing acini to aid in raising intraluminal pressure to facilitate movement of secretory products out of acinus and through ductal system.

Figure 2. Figure 2.

Diagram of formation of acinar lumen in developing salivary gland. A: growing end buds that give rise to acini are solid cellular structures. B: central cells in end bud begin to elongate and form junctional complexes at presumptive luminal end (differentiation of apical domain of cells). C: cytofilament aggregates and myosin ATPase activity appear concentrated beneath membranes at presumptive apical end of cells. D: apparent contraction of apical cytofilaments gives rise to end bud lumen.

Figure 3. Figure 3.

Electron micrograph showing basal portion of typical salivary gland epithelial cell at stage II or III. This particular cell is from developing rat submandibular gland at stage IIIa. Cytoplasm of cell is filled with free polyribosomes. A few strands of endoplasmic reticulum (er) and few scattered mitochondria (M) are in cytoplasm. Cells rest on intact basal lamina (bl). X 10,000.

Figure 4. Figure 4.

Electron micrograph of differentiating submandibular gland acinar cell (stage IV) shortly after direct epithelial‐mesenchymal interactions seen in stage III have taken place. Cell has assumed columnar shape and started to amplify secretory protein synthesis. Cytoplasm is dominated by free polyribosomes with few mitochondria and scattered strands of endoplasmic reticulum. Endoplasmic reticulum is filled with newly synthesized secretory product, causing cisternae to be widely dilated (arrows). X4,250. Inset: high‐magnification electron micrograph of dilated ER cisterna. Ribosomes studding cisternal membrane are clearly visible, as is flocculent material within cisternal lumen. X 30,000.

Figure 5. Figure 5.

Electron micrograph of several differentiated acinar cells (stage V). Cells are from developing submandibular gland acinus at 21 days in utero. Cells show typical apical‐basal polarity of organelles. Nucleus and strands of endoplasmic reticulum are in basal cytoplasm; Golgi, condensing vacuoles, and secretory granules are in more apical cytoplasm. X 4,050.

Figure 6. Figure 6.

Electron micrograph of direct epithelial‐mesenchymal contact (junc) between submandibular gland end bud cell (SMG) at stage IIIb and mesenchymal (MES) fibroblast (Fib). Epithelial cell is extending projection through basal lamina (bl) to contact fibroblast. X 7,100.



Figure 1.

Diagram of major stages in development of salivary glands. Stage I: salivary epithelium begins to grow down from oral epithelium into underlying mesenchyme (MES). Epithelium is separated from mesenchyme by intact basal lamina (BL). Stage II: epithelium continues to proliferate and grow. Mesenchyme condenses to form a discrete capsule. Collagen type I is deposited in proximity to epithelial basal lamina. Stages IIIa and IIIb: specific morphogenetic branching pattern is established through differential cell division at growing ends of branch buds and through changes in synthesis and degradation of basal lamina. Collagen type I stabilizes lamina in clefts but lamina becomes discontinuous at growing ends. Direct epithelial‐mesenchymal interactions occur at growing ends of early branches. Stage IV: branching continues. Cells become polarized and amplify secretory protein synthesis. Stage V: cells initiate packaging of secretory proteins into zymogen granules. Myoepithelial cells (MEC) differentiate at periphery of developing acini to aid in raising intraluminal pressure to facilitate movement of secretory products out of acinus and through ductal system.



Figure 2.

Diagram of formation of acinar lumen in developing salivary gland. A: growing end buds that give rise to acini are solid cellular structures. B: central cells in end bud begin to elongate and form junctional complexes at presumptive luminal end (differentiation of apical domain of cells). C: cytofilament aggregates and myosin ATPase activity appear concentrated beneath membranes at presumptive apical end of cells. D: apparent contraction of apical cytofilaments gives rise to end bud lumen.



Figure 3.

Electron micrograph showing basal portion of typical salivary gland epithelial cell at stage II or III. This particular cell is from developing rat submandibular gland at stage IIIa. Cytoplasm of cell is filled with free polyribosomes. A few strands of endoplasmic reticulum (er) and few scattered mitochondria (M) are in cytoplasm. Cells rest on intact basal lamina (bl). X 10,000.



Figure 4.

Electron micrograph of differentiating submandibular gland acinar cell (stage IV) shortly after direct epithelial‐mesenchymal interactions seen in stage III have taken place. Cell has assumed columnar shape and started to amplify secretory protein synthesis. Cytoplasm is dominated by free polyribosomes with few mitochondria and scattered strands of endoplasmic reticulum. Endoplasmic reticulum is filled with newly synthesized secretory product, causing cisternae to be widely dilated (arrows). X4,250. Inset: high‐magnification electron micrograph of dilated ER cisterna. Ribosomes studding cisternal membrane are clearly visible, as is flocculent material within cisternal lumen. X 30,000.



Figure 5.

Electron micrograph of several differentiated acinar cells (stage V). Cells are from developing submandibular gland acinus at 21 days in utero. Cells show typical apical‐basal polarity of organelles. Nucleus and strands of endoplasmic reticulum are in basal cytoplasm; Golgi, condensing vacuoles, and secretory granules are in more apical cytoplasm. X 4,050.



Figure 6.

Electron micrograph of direct epithelial‐mesenchymal contact (junc) between submandibular gland end bud cell (SMG) at stage IIIb and mesenchymal (MES) fibroblast (Fib). Epithelial cell is extending projection through basal lamina (bl) to contact fibroblast. X 7,100.

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Leslie S. Cutler. Functional Differentiation of Salivary Glands. Compr Physiol 2011, Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion: 93-105. First published in print 1989. doi: 10.1002/cphy.cp060306