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Dr. Aravind, Jamaica
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DEVELOPMENT OF SALIVARY GLANDS

·        The ontogenetic development of glandular tissue - Epithelial-Mesenchymal interactions.

·       The mesenchyme – role in both the initiation and growth of the glandular bud & also the cytodifferentiation of glandular cells.

·         The functional glandular tissue develops as an epithelial outgrowth of the buccal epithelium, which invades the underlying mesenchyme.

·         Individual salivary glands – proliferation of oral epithelial cells – form a focal thickening that grows into the underlying ectomesenchyme.

·         Continued growth formation of a small bud connected to the surface by a trailing cord of epithelial cells.

·         The mesenchymal cells condense around the bud.

·         Clefts develop in the bud, forming two or more new buds.

·         A continuation of this process, called branching morphogenesis successive generations of the buds and a hierarchic ramification of the gland.

·         The connective tissue stroma (capsule & septa) & blood vessels  from the mesenchyme.

·         Signaling molecules – members of the FGF protein family; Shh; TGF-β; & their receptors – major role in the development of branches.

·         As the epithelial bud forms, those portions of the bud closest to the stomodeum differentiate into the main excretory duct of the gland – the most distal portions of the bud form the secretory end pieces or acini.

·         The origin of the epithelial buds – ectodermal – parotid & minor salivary glands; and endodermal – submandibular and sublingual glands.

·         The differential contraction of actin filaments at the basal & apical ends of the epithelial cells – provides the physical mechanism, underlying the formation of the cleft.

·         The deposition of extracellular matrix components within the clefts, serves to stabilize them.

·         The development of a lumen within the branched epithelium – occurs 1st in distal end of the main cord & in branch cords.

·         Then in the proximal end of the main cord, & finally in the central portion of the main cord.

·         The lumina form within the ducts before they develop within the terminal buds.

·         Studies – the lumen formation – apoptosis of centrally located cells in the cell cords.

·         After the lumen is developed in the terminal buds, the epithelium – 2 layers of cells.

·         The cells of the inner layer – finally differentiate into the secretory cells of the mature gland (either mucous or serous).

·         Cells of the outer layer – contractile myoepithelial cells around the secretory end pieces and intercalated ducts.

·         As the epithelial parenchymal components increase in size and number – associated mesenchyme (connective tissue) is diminished.

·         A thin layer of connective tissue remains, surrounding each secretory end piece & duct of the adult gland.

·         Thicker partitions of connective tissue (septa) – continuous with the capsule, invest the excretory ducts & divide the gland into lobes and lobules.

·         The parotid glands – corners of the stomodeum - 4th to 6th week of embryonic life.

·         The submandibular glands – floor of the mouth at the end of the 6th week or the beginning of the 7th week in utero.

·         The sublingual gland – lateral to the submandibular primordium at 8th week, IUL

·         The minor salivary glands bud from the buccal epithelium – 8 to 12 weeks of the embryonic life.

·         The cells of the secretory end pieces & ducts attain maturity – last 2 months of gestation.

·         The glands continue to grow post-natally, upto 2 years of age. 

STAGES OF DEVELOPMENT: 6 stages 

STAGE I: BUD FORMATION:

·         Induction of Oral Epithelium by Underlying Mesenchyme – results in tissue thickening and bud formation.

·         The growing bud is separated from the condensation of mesenchyme by a basal lamina.

STAGE II: FORMATION AND GROWTH OF EPITHELIAL CORD:

·         A solid cord of cells – from epithelial bud by cell proliferation.

·         Condensation and proliferation – in the surrounding mesenchyme, closely associated with the epithelial cord.

·         The basal lamina is found between the cord and the mesenchyme.

·         It is composed of glycosaminoglycans, collagen, and glycoprotein.

·         It plays a role in influencing morphogenesis and differentiation of the salivary glands throughout their development.

STAGE III: INITIATION OF BRANCHING IN TERMINAL PARTS OF EPITHELIAL CORD AND CONTINUATION OF GLANDULAR DIFFERENTIATION:

·         The epithelial cord proliferates rapidly & branches into terminal bulbs (presumptive acini).

·         The growth in length of the solid epithelial cords & the differentiation of the berry-like, terminal bulbs occurs in this stage.

STAGE IV: DICHOTOMOUS BRANCHING OF EPITHELIAL CORD AND LOBULE FORMATION:

·         The branching continues at the terminal portions of the cord – extensive tree-like system of bulbs.

·         Connective tissue differentiates around the branches – extensive lobulation.

·         The glandular capsule – from mesenchyme and surrounds the entire glandular parenchyma.

STAGE V:  CANALIZATION OF PRESUMPTIVE DUCTS:

·         Canalization of the epithelial cord – a hollow tube or duct, by the 6th month in all three major salivary glands.

·         Two main theories to explain the mechanism of canalization:

o   Different rates of cell proliferation between the outer and inner layers of the epithelial cord.

o   Fluid secretion by the duct cells increases the hydrostatic pressure and produces a lumen within the cord.

STAGE VI: CYTODIFFERENTIATION:

·         Final stage of salivary gland development – histodifferentiation of the functional acini and intercalated ducts.

·         Mitotic activity shifts from the epithelial cord to the terminal bulb portion.

·         The initiation of cytodifferentiation of salivary gland acinar cells is dependent on pre-programmed development occurring in early stages of morphogenesis.

·         Epithelial-mesenchymal contact – for cytodifferentiation.

·         Once this contact takes place, exocrine cell differentiation occurs in the absence of mesenchyme.

·         There is a “partial coupling" of the independently controlled processes of gland morphogenesis and cytodifferentiation.

·         Full differentiation of functional secretory components – apparent at birth – not complete until the onset of a solid diet & the presence of masticatory stimuli.