Salivary Gland Development

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Introduction

Adult Gastrointestinal Tract

The salivary glands arise as epithelial buds in the oral cavity between week 6 to 7 (GA week 8 to 9) and extend into the underlying mesenchyme. The three paired groups of salivary glands are named by their anatomical location: parotid, submandibular and sublingual.


The adult glands are mucoserous tubuloacinar glands, with secretory acini and the initial part of the duct system also participates in the secretory process.Secretions from glands close to the oral cavity are mainly mucous, while glands located further away from the oral cavity (parotid) are mainly serous. Structurally, each salivary gland is divided by connective tissue septa into lobes, which are in turn subdivided into lobules.


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1878 Alimentary Canal | 1882 The Organs of the Inner Germ-Layer The Alimentary Tube with its Appended Organs | 1884 Great omentum and transverse mesocolon | 1902 Meckel's diverticulum | 1902 The Organs of Digestion | 1903 Submaxillary Gland | 1906 Liver | 1907 Development of the Digestive System | 1907 Atlas | 1907 23 Somite Embryo | 1908 Liver | 1908 Liver and Vascular | 1910 Mucous membrane Oesophagus to Small Intestine | 1910 Large intestine and Vermiform process | 1911-13 Intestine and Peritoneum - Part 1 | Part 2 | Part 3 | Part 5 | Part 6 | 1912 Digestive Tract | 1912 Stomach | 1914 Digestive Tract | 1914 Intestines | 1914 Rectum | 1915 Pharynx | 1915 Intestinal Rotation | 1917 Entodermal Canal | 1918 Anatomy | 1921 Alimentary Tube | 1932 Gall Bladder | 1939 Alimentary Canal Looping | 1940 Duodenum anomalies | 2008 Liver | 2016 GIT Notes | Historic Disclaimer
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Animal Development: 1913 Chicken | 1951 Frog

Some Recent Findings

  • Fgf10 and Sox9 are essential for the establishment of distal progenitor cells during mouse salivary gland development[1] "Salivary glands are formed by branching morphogenesis with epithelial progenitors forming a network of ducts and acini (secretory cells). During this process, epithelial progenitors specialise into distal (tips of the gland) and proximal (the stalk region) identities that produce the acini and higher order ducts, respectively. Little is known about the factors that regulate progenitor expansion and specialisation in the different parts of the gland. Here, we show that Sox9 is involved in establishing the identity of the distal compartment before the initiation of branching morphogenesis. Sox9 is expressed throughout the gland at the initiation stage before becoming restricted to the distal epithelium from the bud stage and throughout branching morphogenesis. Deletion of Sox9 in the epithelium results in loss of the distal epithelial progenitors, a reduction in proliferation and a subsequent failure in branching. We demonstrate that Sox9 is positively regulated by mesenchymal Fgf10, a process that requires active Erk signalling. These results provide new insights into the factors required for the expansion of salivary gland epithelial progenitors, which can be useful for organ regeneration therapy."
  • Anatomy and histology of rodent and human major salivary glands[2] "Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands."
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<pubmed limit=5>Salivary Gland Development</pubmed>

Salivary Ducts

Gland duct histology cartoon.jpg

Gland ducts

intercalated -> striated -> excretory -> main excretory ducts

  • Intercalated duct - region close to acinar neck are thought to contain salivary gland stem cells.

Parotid Gland

Overview neck region (week 8) Parotid gland (week 8)
Human embryo neck 02.jpg Human embryo neck 03.jpg
Parotid gland primordial of capsule propia (arrowheads).
  • C - Meckel’s cartilage
  • CL - Cervical lamina
  • I - Inferior alveolar nerve
  • L - Lingual nerve
  • M - Mandible
  • MS - Masseter muscle
  • P - Anlage of the parotid gland

Anatomy

Parotid Gland

  • largest salivary gland
  • located in the triangle surrounded by:
    • superiorly by the zygomatic arch
    • anteriorly by the masseter
    • posteriorly by the sternocleidomastoid
  • inferior pole mostly confined to the angle of mandible.
  • medial pole mostly confined to the temporomandibular joints.
  • parotid duct (Stenon’s duct) leaves the anterior border, passes anteriorly on the masseter, penetrates the buccinator, and opens into the buccal cavity.
    • named after Niels Stensen (1638 - 1686) a Danish anatomist, natural scientist, and theologist.
  • facial nerve (CN VII) penetrates the gland

Sublingual Gland

  • locate superior of the mylohyoid
  • superior border of sublingual gland appears as the sublingual fold in the oral floor.
  • major sublingual duct (Bartholin’s duct) opens in the sublingual caruncle.
  • numerous minor sublingual ducts on the sublingual fold.

Submandibular Gland

  • locate inferior space of the mylohyoid.
  • submandibular duct (Wharton’s duct)
    • runs forward along the lingual nerve in the sublingual space
    • opens in the sublingual caruncle

Lingual Gland

lingual gland
  • Mucous glands are similar in structure to the labial and buccal glands. They are found especially at the back part behind the vallate papillæ, but are also present at the apex and marginal parts. In this connection the anterior lingual glands (Blandin or Nuhn) require special notice. They are situated on the under surface of the apex of the tongue, one on either side of the frenulum, where they are covered by a fasciculus of muscular fibers derived from the Styloglossus and Longitudinalis inferior. They are from 12 to 25 mm long, and about 8 mm. broad, and each opens by three or four ducts on the under surface of the apex.
  • Serous glands (von Ebner's gland) occur only at the back of the tongue in the neighborhood of the taste-buds, their ducts opening for the most part into the fossæ of the vallate papillæ. These glands are racemose (clustered), the duct of each branching into several minute ducts, which end in alveoli, lined by a single layer of more or less columnar epithelium. Their secretion is of a watery nature, and probably assists in the distribution of the substance to be tasted over the taste area.

(text modified from Gray's anatomy)

Animal Models

Mouse

Submandibular salivary gland developmental timeline data below from [3]

  • E11.5 - thickening of the primitive oral epithelium that grows into the first branchial (mandibular) arch mesenchyme to form the solid epithelial placode.
  • E12 - placode protrudes into the mesenchyme forming a single, solid mass of cells connected to the tongue epithelium by a stalk of immature duct epithelial cells.
  • E12.5 - indentations (clefts) start to form on the surface of the epithelial bud accompanied by alterations in the basement membrane. Clefts separate the primary bud into multiple buds and the epithelium proliferates. The base of the cleft becomes the primordial ductal structure, salivary branching morphogenesis is repeated multiple times over the following days.
  • E14 - simple one-bud one-duct salivary gland has both grown and branched significantly, and the main duct begins to lumenize. The end buds undergo reorganization and begin to form acini – the main secretory units of the salivary gland.
  • E15E16 - lumenization of the main secretory duct is nearly complete.
  • E17 - the acini complete lumenization, so that the gland has a continuous network of lumenized ducts connecting the acini to the oral cavity. Both nerves and blood vessels populate the gland in association with the branching epithelium.
  • Glands continue to mature after birth with cellular differentiation occurs in parallel with branching morphogenesis.


Links: Mouse Development

Molecular

Recent studies have identified similar molecular mechanisms for salivary gland branching as used for development of the respiratory system branching using FGF10 and Sox9.

FGF10

Wnt and Fibroblast growth factor 10 (Fgf10) receptors combine with Kit signalling to promote the expansion of the distal tip cells.

Links: Fibroblast Growth Factor

SOX9

Sox9 establishes the identity of the developing gland distal compartment before the initiation of branching morphogenesis.[1]


Histology

Submandibular gland

  • mixed salivary gland
  • predominantly serous acini; some mucous acini with serous demilunes
  • short intercalated ducts.
  • striated ducts with simple cuboidal lining epithelium.
  • interlobular ducts with stratified cuboidal or stratified columnar epithelium surrounded by connective tissue.
Submandibular gland histology 03.jpg

Sublingual gland

  • mixed salivary gland
  • predominantly mucous acini; some serous demilunes.
  • acini are composed of centrally-located mucous cells and peripheral serous demilunes.
  • short intercalated ducts.
  • striated ducts with simple columnar lining epithelium
  • interlobular ducts with stratified cuboidal/columnar epithelium, surrounded by connective tissue.


Sublingual gland histology 02.jpg

Sublingual gland histology 01.jpg

Parotid gland

  • serous salivary gland
  • serous acini, zymogen granules
  • intercalated ducts
  • striated ducts
  • interlobular ducts with stratified epithelium.
  • lobules with connective tissue septa.
  • nearby lymph node with capsule.
Parotid gland histology 01.jpg

Parotid histology stratified columnar 01.jpg

Parotid gland histology 05.jpgParotid gland histology 06.jpg

Parotid gland histology 03.jpgParotid gland histology 04.jpg

Lingual salivary gland

Tongue histology 05.jpg

Circumvallate Papilla

Tongue histology 02.jpg

Human Tongue ( lingual salivary gland, white adipose tissue, skeletal muscle)


Abnormalities=

Cystic Fibrosis

The absence of the transmembrane conductance regulator (CFTR) affects not only respiratory tract exocrine secretion, but also secretion in salivary glands. In the mouse, CFTR expression begins at E15 and within ducts but not in acini.[4]

Primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) results in the destruction of the salivary and the lacrimal glands through by mononuclear cell infiltration.[5]


References

  1. 1.0 1.1 Chatzeli L, Gaete M & Tucker AS. (2017). Fgf10 and Sox9 are essential for the establishment of distal progenitor cells during mouse salivary gland development. Development , 144, 2294-2305. PMID: 28506998 DOI.
  2. Amano O, Mizobe K, Bando Y & Sakiyama K. (2012). Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-. Acta Histochem Cytochem , 45, 241-50. PMID: 23209333 DOI.
  3. Larsen M, Yamada KM & Musselmann K. (2010). Systems analysis of salivary gland development and disease. Wiley Interdiscip Rev Syst Biol Med , 2, 670-82. PMID: 20890964 DOI.
  4. Shin YH, Lee SW, Kim M, Choi SY, Cong X, Yu GY & Park K. (2016). Epigenetic regulation of CFTR in salivary gland. Biochem. Biophys. Res. Commun. , 481, 31-37. PMID: 27833020 DOI.
  5. Aqrawi LA, Jensen JL, Øijordsbakken G, Ruus AK, Nygård S, Holden M, Jonsson R, Galtung HK & Skarstein K. (2018). Signalling pathways identified in salivary glands from primary Sjögren's syndrome patients reveal enhanced adipose tissue development. Autoimmunity , , 1-12. PMID: 29504848 DOI.


Reviews

Articles

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Search term: Head Development | Parotid Development | Submandibular Gland Development | Sublingual Gland Development


Terms

Abbreviations: ( ) plural form in brackets, A. Arabic, abb. abbreviation, c. circa =about, F. French adj. adjective, G. Greek, Ge. German, cf. compare, L. Latin, dim. diminutive, NA. Nomina anatomica, q.v. which see, OF. Old French

  • acinus (-i) - L. = a juicy berry, a grape; applied to small, rounded terminal secretory units of compound exocrine glands that have a small lumen (adj. acinar).
  • Bartholin’s duct - see sublingual duct.
  • buccal - L. bucca = cheek; related to cheek or mouth.
  • circumvallate papillae - (vallate papillae) tongue largest and least numerous papillae (human 8 to 12) occur in depressions of the surface of the tongue and are surrounded with a trench formed by the infolding of the epithelium. Taste buds are numerous on the lateral surfaces of these papillae and the excretory ducts of serous glands (glands of von Ebner) open into the trenches surrounding the papillae.
  • demilune - L. dimidius = half + luna = moon; crescent-shaped cap of serous cells over mucous alveolus in some salivary glands.
  • ductus (-us) - L. = passage from L. ducere = to lead; tube lined by epithelium for exocrine glandular secretions to reach surface.
  • filiform papillae - tongue smallest and most numerous papillae, provide a rough surface to aid in the manipulation and processing of foods.
  • fungiform - L. fungus = mushroom + forma = a shape; of lingual papillae.
  • fungiform papillae - tongue single evenly spaced between the filiform papillae. Epithelium is slightly thinner than on the remaining surface of the tongue and connective tissue core is richly vascularised.
  • gland - L. glandula , dim of L. glans = an acorn, a pellet; term used to describe mesenteric lymph nodes (Herophilus, c. 300 BC).
  • intercalated - L. inter = between + calare = to proclaim, calatus = inserted; of a duct inserted between the end of the gland (acinus, or alveolus) and a larger duct. Partially covered by myoepithelial cells
  • intercalated duct - cuboidal epithelium, modify saliva, add bicarbonate ions (buffering) and absorb chloride.
  • intramural - L. intra = within + murus = wall; within the wall of an organ.
  • labial - adj. L. labialis = of the lips, L. labium = lip, rim of a vessel.
  • lacteal - L. lac = milk ( lacteus = of milk, lactare = to suckle); intestinal lymphatic, containing chyle after a fatty meal.
  • lining epithelium - non-keratinised stratified squamous epithelium, covers the remaining (non-masticatory epithelium) surfaces of the oral cavity.
  • lingual - adj. L. lingua = tongue.
  • lips - outside (lined by skin) and inside (oral mucosa), vermilion border (prolabium) transition from the skin to the oral mucosa, forms only small part of the anatomical lips.
  • lumen - L. = light; space enclosed by tubular or vesicular structure; hence luminal.
  • masticatory epithelium - covers the tongue, gingivae and hard palate. Keratinised epithelium to different degrees depending on the extent of physical forces exerted on the epithelium.
  • microvilli - epithelial cell apical surface specialisation seen in the small intestinal. These microfilament filled structures increase the surface area for absorption and secretion.
  • mucin - L. mucus from G. muxa = snot, slime; protein constituent of all mucus; occurs as granules in secretory cells.
  • mucosa - (-ae) L. = mucous membrane.
  • mucus - L. = slime (adj. mucous).
  • oesophagus - G. oiso = future of phero = I carry + pahgein = to eat; G. oisophagos = gullet, or tube carrying food from pharynx to stomach.
  • oesophageal glands - located in the submucosa produce a mucous secretion, which lubricates the epithelium and aids the passage of food. Oesophagus closest to the stomach may also be mucosal mucus-producing glands, similar to the glands in the adjacent mucosa of the stomach.
  • oral - adj. L. os, oris = mouth.
  • palate - L. palatum = roof of mouth.
  • palisade - L. palus = stake; like a fence of stakes.
  • papilla - (-ae) L. = a teat, a nipple; a nipple-like projection, e.g., on the tonge (Malpighi, c. 1670; cf. circumvallate, filiform, foliate, fungiform, vallate); duodenal papilla (containing duodenal ampulla).
  • parotid - G. para = beside + otos = of the ear; a salivary gland.
  • parotid duct - (Stenson's duct) the major duct of the parotid gland that allows salivary gland secretions to empty into the oral cavity.
  • ruga - (-ae) L. = a fold or wrinkle, e.g., in stomach.
  • sac - L. saccus = sack, bag, from G. sakkos .
  • salivary - L. saliva = spittle.
  • secretion - L. secretus = separated; production of materials by glandular activity.
  • serous - adj. L. = having nature of serum, watery fluid.
  • Stenson's duct - see parotid duct. Named after Niels Stensen (1638 - 1686) a Danish anatomist, natural scientist, and theologist.
  • striated ducts - modifies saliva (secretion of potassium and the absorption of sodium), columnar cells with the nucleus of located approximately midways between the apical and basal cell surfaces. Striations are found in the basal part of the cytoplasm of the cells, where numerous mitochondria are found between infoldings of the basal cell membrane. These cells can also take up a secretable form of antibodies and release them into the saliva.
  • sublingual caruncle - location on either side of the frenulum linguae on the sublingual surface of the tongue.
  • sublingual duct - (major sublingual duct, Bartholin’s duct) from the sublingual gland that opens in the sublingual caruncle. There are also numerous minor sublingual ducts opening on the sublingual fold.
  • submandibular - adj. L. " + mandibula = jaw.
  • submandibular duct - (Wharton’s duct) from the submandibular gland, runs forward along the lingual nerve in the sublingual space and opens in the sublingual caruncle.
  • tongue muscles - skeletal muscle organized into strands oriented more or less perpendicular to each other.
  • tongue nerves - movement (XII, hypoglossal nerve - motor) and sensory information. (V, trigeminal nerve - sensory - anterior two-thirds; VII, facial nerve - taste; IX, glossopharyngeal nerve - sensory/taste - posterior one-third).
  • tonsil - L. tonsilla (origin obscure); mass of lymphocytes close to an epithelium, e.g., lingual tonsil, palatine tonsil (the "tonsil"), pharyngeal tonsil (adenoid, tonsil of Luschka, q.v.), tubal tonsil (of auditory tube).
  • tubuloacinar gland - secretory acini with the first part of the duct system also participating in the secretory process.
  • vallate papillae - see circumvallate papillae.
  • von Ebner's glands - serous glands associated with circumvallate papillae, their ducts open into the trenches surrounding the papillae ("rinsing glands").
  • Wharton’s duct - see submandibular duct. Named after Thomas Wharton (1614–1673) an English anatomist also known for umbilical cord Wharton’s jelly.


GIT Links: Introduction | Medicine Lecture | Science Lecture | endoderm | mouth | oesophagus | stomach | liver | gallbladder | Pancreas | intestine | mesentery | tongue | taste | enteric nervous system | Stage 13 | Stage 22 | gastrointestinal abnormalities | Movies | Postnatal | milk | tooth | salivary gland | BGD Lecture | BGD Practical | GIT Terms | Category:Gastrointestinal Tract
GIT Histology Links: Upper GIT | Salivary Gland | Smooth Muscle Histology | Liver | Gallbladder | Pancreas | Colon | Histology Stains | Histology | GIT Development
Historic Embryology - Gastrointestinal Tract  
1878 Alimentary Canal | 1882 The Organs of the Inner Germ-Layer The Alimentary Tube with its Appended Organs | 1884 Great omentum and transverse mesocolon | 1902 Meckel's diverticulum | 1902 The Organs of Digestion | 1903 Submaxillary Gland | 1906 Liver | 1907 Development of the Digestive System | 1907 Atlas | 1907 23 Somite Embryo | 1908 Liver | 1908 Liver and Vascular | 1910 Mucous membrane Oesophagus to Small Intestine | 1910 Large intestine and Vermiform process | 1911-13 Intestine and Peritoneum - Part 1 | Part 2 | Part 3 | Part 5 | Part 6 | 1912 Digestive Tract | 1912 Stomach | 1914 Digestive Tract | 1914 Intestines | 1914 Rectum | 1915 Pharynx | 1915 Intestinal Rotation | 1917 Entodermal Canal | 1918 Anatomy | 1921 Alimentary Tube | 1932 Gall Bladder | 1939 Alimentary Canal Looping | 1940 Duodenum anomalies | 2008 Liver | 2016 GIT Notes | Historic Disclaimer
Human Embryo: 1908 13-14 Somite Embryo | 1921 Liver Suspensory Ligament | 1926 22 Somite Embryo | 1907 23 Somite Embryo | 1937 25 Somite Embryo | 1914 27 Somite Embryo | 1914 Week 7 Embryo
Animal Development: 1913 Chicken | 1951 Frog


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Cite this page: Hill, M.A. (2024, March 28) Embryology Salivary Gland Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Salivary_Gland_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G