Salivary Gland Development Flashcards
Salivary glands develop through reciprocal interactions between
epithelium and underlying mesenchyme
3 processes of salivary gland organogenesis
positional information, morphogenesis, differentiation
Assembly of multicellular salivary glands involves
cell shape changes, cell migration, axis elongation during duct formation and changes on tissue specific gene expression
Branching morphogenesis in mammalian salivary glands require
reciprocal epithelium-mesenchyme interactions that result in repetitive clefting, new bud formation and branching
Organs that develop by branching morphogenesis through reciprocal epithelial-mesenchyme tissue interactions (6)
tooth, hair, kidney, lung, mammary gland, salivary gland
Where do salivary glands originate from? (submandibular, parotid, sublingual)
primitive gut endoderm (submandibular)
ectoderm-derived surface epithelium (parotid and sublingual)
During branching morphogenesis, progenitor cells undergo these processes to form specialized salivary cell types
maintenance, proliferation, lineage commitment, differentiation
Salivary glands comprised of these cell types
epithelial, myoepithelial, mesenchymal, neuronal, endothelial.
These cell types must interact for normal function.
Function of myoepithleial cells in salivary glands
Facilitates secretion of saliva (stimulated by neuronal cells)
k19 cells
Cells that will eventually will be in middle of duct forming lumen of duct
Fibronectin formed by what cell types?
Epithelial and mesenchymal
How does fibronectin specify shape of salivary epithelium?
Accumulation of fibronectin (via secretion in epithelium and deposited by mesenchymal compartment) specifies cleft, lowest concentration of fibronectin at bud region
Laminin
- interacts with integrins in basal region
- regulate developmental processes
- follows formation of new ducts
FGF signalling
- required for branching morphogenesis
- inhibition of Fgfr1 expression decreases branching morphogenesis (probably more detail than needed)
Inner bud cells differentiate to form ___, while outer bud cells differentiate to form ___ during salivary gland development
Inner differentiate to form ductal structures, outer differentiate to form acinar cells.
F actin important in which aspect of salivary gland development?
Duct development. Collaborates with ZO-1 to elongate ductal axis for duct extension
ZO-1
distrubuted asymmetrically to set up polarity in apical domains in inner bud cells on duct forming regions of the bud
Parasympathetic innervation regulates _____
tubulogenesis in developing salivary gland and further development of duct formation
tubulogenesis
formation of ductal structures during branching morphogenesis, involving assembly of cells into a tubular network
microlumen
A small lumen which is formed during tubulogenesis, which will eventually fuse with other microlumens to form a single large lumen
K19+ cells
Proliferate and condense to form microlumens
Vasoactive intestinal peptide (VIP)
regulates key steps in tubulogenesis:
- duct elongation through proliferation
- fusion of microlumens
Once lumen is formed, required for lumen expansion
NRTN
important in bringing neuronal cell into involvement of salivary gland formation
E-cadherin
- cell-cell adhesion molecule
- required for survival of differentiating duct cells and for maintenance of lumens
- tumor suppressor: suppresses abnormal growth
Polarity of cells maintained by
Maintained by junctional proteins in developing tissues
Inhibition of E-cadherin would cause:
dilated and abnormal lumen formation
Hippo signalling pathway
interacts with E-cadherin cell-cell adhesion receptor to drive normal duct formation
key regulator/suppressor of many diseases (like cancer).
TAZ and YAP
- transcription factors in Hippo pathway
- inappropriate nuclear localization can cause abnormal expression of genes (cause pro-growth, etc)
- increase expression during SMG development
- inhibition of YAP prevents branching morphogenesis
Sjogren’s Syndrome
- disregulatoin of cell polarity, E-cadherin junctions and nuclear localization of YAP seen in diseased salivary glands
- autoimmune disease
- impaired salivary flow and fatigue
- increased levels of vimentin, aSMA, CTGF, fibronectin
Fibrosis
Leads to stiffening of tissues and loss of normal body functions. Often seen in head and neck radiation therapy when patients cannot swallow properly afterwards