**3. Development of the salivary glands**

divides into a larger part superficial to the muscle and a smaller part lying deep to the muscle [4]. The submandibular gland duct, also known as Wharton's duct, is thin-walled, about 5 cm long, and runs forward above the mylohyoid muscle lying just below the mucosa of the floor of the mouth in its terminal portion. The duct opens on the floor of the mouth, on the summit of the sublingual papilla also called the caruncula sublingualis, lateral to the lingual frenulum [2].

It is the smallest of all the three major salivary glands that is almond shaped and weighs about 3–4 g. The gland lies above the mylohyoid, below the mucosa of the floor of the mouth, medial to the sublingual fossa of the mandible, and lateral to the genioglossus [4]. It comprises of one main gland duct with various small ducts. The main duct, Bartholin's duct, opens with or near the submandibular duct. Several smaller ducts, duct of Rivinus, open independently

The minor salivary glands are placed below the epithelium in almost all parts of the oral cavity. These glands comprise numerous small groups of secretory units opening via short ducts directly into the mouth. They lack a distinct capsule, instead mixing with the connective tissue

These glands are present on the lips and cheeks and comprise of mucous tubules with serous

These are located to the region of the isthmus in the glossopalatine fold but may extend from

These are located in the glandular aggregates present in the lamina propria of the posterolat-

The glands of the tongue can be divided into various groups [1, 2]. The anterior lingual glands (glands of Blandin and Nuhn) are present near the apex of the tongue. The ducts open on the ventral surface of the tongue near the lingual frenulum. The posterior lingual mucous glands are present lateral and posterior to vallate papillae and in association with lingual tonsil. The ducts of these glands open on the dorsal surface of the tongue. The posterior lingual serous glands (von Ebner's glands) are located between the muscle fibers of the tongue below the vallate papillae, and the ducts open into the trough of circumvallate papillae and at the rudi-

the posterior extension of the sublingual gland to the glands of the soft palate [1, 2].

eral aspect of the hard palate and in the submucosa of the soft palate and uvula [1, 2].

of the submucosa or muscle fibers of the tongue or cheeks [2].

*2.1.3. Sublingual gland*

66 Histology

along the sublingual fold [2].

**2.2. Minor salivary glands**

*2.2.1. Labial and buccal glands*

*2.2.2. Glossopalatine glands*

demilunes [1, 2].

*2.2.3. Palatine glands*

*2.2.4. Lingual glands*

mentary folate papillae on the sides of the tongue.

The development of the glandular tissue involves the interaction of the epithelium with the underlying mesenchyme to form the functional part of the tissue [5, 6]. These epithelialmesenchymal interactions are also known as secondary induction in which the mesenchyme is in close proximity with the epithelium and is required for the normal development of the epithelium. For example, epithelial-mesenchymal interactions regulate both the initiation and growth of the glandular tissue and the eventual cytodifferentiation of cells within the salivary glands. The mesenchyme, therefore, is required for normal development as well as formation of the supporting part of the adult gland.

All salivary glands follow a similar development pattern. The functional glandular tissue (parenchyma) develops as an epithelial outgrowth (glandular bud) of the buccal epithelium that invades the underlying mesenchyme. The connective tissue stroma (capsule and septa) and blood vessels form from the mesenchyme. The mesenchyme is composed of cells derived from neural crest and is important for the normal differentiation of the salivary glands.

As the bud formation begins during development, the portion of the bud closest to the stomodeum eventually differentiates into the main excretory duct of the gland, while the most distal portion of the bud forms the secretory endpieces or acini. The origin of the epithelial buds is believed to be ectodermal in the parotid and minor salivary glands but endodermal in origin in the submandibular and sublingual glands. The parotid gland originates near the corners of the primitive oral cavity by the sixth week of prenatal life. The submandibular glands arise from the floor of the mouth at the end of the sixth or the beginning of the seventh week in utero. The sublingual gland forms lateral to the submandibular primordium at about eighth week. All the minor salivary glands bud from buccal epithelium but start after their 12th prenatal week.

Stages of development [5, 6]


producing extensive lobulation. The glandular capsule forms from mesenchyme and surrounds the entire glandular parenchyma.

**Mucous cells**: The secretory endpieces that are composed of mucous cells typically have a tubular configuration; when cut in cross section, these tubules appear as round profiles with mucous cells surrounding central lumen of larger size than that of serous endpieces. The nucleus is oval or flattened in shape and located above the basal plasma membrane. Sometimes, mucous cells have bonnet- or crescent-shaped appearance, which is made up of serous cells and are also known as demilunes first described by Giuseppe Oronzo Giannuzzi in 1865. The presence of demilunes is not clearly known, but these demilunes occur as a result of artifact during tissue preparation. Nowadays, recent studies like rapid freezing, freeze substitution, and three-dimensional reconstruction techniques have shown that serous cells align with mucous cells to surround a common lumen. The mucous cells show accumulation of large amounts of secretory product that pushes the nucleus and endoplasmic reticulum

Salivary Glands

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http://dx.doi.org/10.5772/intechopen.81213

The mucous secretion differs from secretion of serous in two important aspects:

• The secretion of mucous cells has little or no enzymatic activity and is responsible mainly

• The ratio of carbohydrates to protein is greater, and large amount of sialic acid and occa-

In routine histological sections, the secretion of mucous cell appears unstained, and they are strongly stained when special stains like PAS, alcian blue, mucicarmine, etc. are used [1].

These are the contractile cells associated with secretory endpiece and intercalated duct of the salivary glands. These cells are present between the basal lamina and the secretory or duct cells and are joined to the cells by desmosomes. They appear similar to smooth muscle but are derived from the epithelium. They are also known as basket cells or octopus sitting on a rock. The myoepithelial cells located around the secretory endpieces have stellate-shaped, numerous branching processes with a flattened nucleus and scanty perinuclear cytoplasm, but the cells associated with intercalated ducts have more fusiform shape and are elongated with fewer processes. These cells accelerate the initial flow of saliva from the acini, reduce luminal volume, support the underlying parenchyma, reduce the back permeation of fluid, and also help to maintain the patency. They maintain the cell polarity and structural organization of cells. They secrete various tumor suppressor proteins such as protease inhibitors and antian-

It consists of hollow tubes that connect initially with the acinus, i.e., secretory endpieces, and extends to the oral cavity. It is not a pipeline or conduit for the passageway for the saliva, but

• **Intralobular ducts**: Those ducts which are within the lobule. The intercalated and striated

giogenesis factors which provide a barrier against invasive epithelial neoplasm.

it actively participates in the production and modification of saliva.

On the basis of location, ducts are of two types:

ducts are intralobular ducts.

against the basal cell membrane.

**4.2. Myoepithelial cells**

**4.3. Ducts**

for lubrication and protection of the oral tissues.

sionally sulfated sugars are present [2].

**V. Canalization of presumptive ducts:** Canalization of the epithelial cord, with the formation of a hollow tube or duct, usually occurs by the sixth month in all the major salivary glands.

The two main theories to explain the mechanism of canalization are:


Parasympathetic nerves play an important role in epithelial tubulogenesis in the developing salivary gland which involve epithelial-mesenchymal interaction. The neurotransmitter, i.e., vasoactive intestinal peptide (VIP) and its receptor VIPR1, regulates various steps like epithelial proliferation, duct elongation, and lumen formation through cAMP or protein kinase A (PKA) pathway, thus linking epithelial tubulogenesis with parasympathetic neuronal function. Neurotrophic factor neurturin (NRTN), secreted by the buds, binds its receptor GFR alpha 2 and promotes functional nerve outgrowths to ensure parallel development of nerves and epithelium. Cystic fibrosis transmembrane conductance regulator (CFTR) causes lumen expansion during development [7].
