Table 1.
Bona fide and putative salivary gland progenitors
| Progenitor cell marker | Lineages traced in developing/adult organs | Phenotype from gene ablation/mutation |
|---|---|---|
| ASCL3 | SG - Constitutively active Cre labels duct and acinar cells (Arany, et al., 2011; Bullard, et al., 2008; Rugel-Stahl, et al. 2012) | SG - No phenotype in Ascl3-deficient SG (Arany, et al., 2011) |
| Olfactory epithelium – gives rise to microvillar cells and Bowman’s gland (Yoshida, et al., 2001; Weng, et al. 2016) | Olfactory epithelium - Ascl3-deficient mouse lacks the non-neuronal microvillar and Bowman’s gland support cells (Weng, et al. 2016) | |
| KIT | SG – duct cells (adult reported; Emmerson et al., 2018). | SG - Kit-deficient E14 SG (Kitw/w) has reduced epithelial branching (Lombaert, et al., 2013) |
|
Olfactory epithelium (Goss, et al. 2015) Lymphatics (Stanczuk, et al. 2015) |
Kidney - reductions in ureteric bud branching and nephrons (Kitw/w and via inhibition of c-kit tyrosine phosphorylation; Schmidt-Ott, et al., 2006) | |
| KRT5 | SG - acini, ducts, myoepithelial cells of fetal gland (adult not reported; Knox, et al., 2010) | SG - No Krt5-deficient SG studies reported |
|
Lacrimal gland – duct and myoepithelial cells in adult gland (fetal not reported; Farmer et al. 2017) Developing trachea and lung airway epithelia (Rock, et al. 2009) |
Skin – Krt5(−/−) die shortly after birth and exhibit skin blistering arising from basal cell cytolysis (Peters et al. 2001) Human mutations in KRT5 and KRT14 cause Epidermolysis bullosa simplex (Peters et al. 2001) |
|
| KRT14 | SG – acini (fetal only), ducts, myoepithelial cells (fetal and adult) (Lombaert, et al. 2013; Patel, et al., 2014; Kwak, et al. 2016) | SG - No Krt14-deficient SG studies reported |
|
Skin (Mascre, et al. 2012) Cornea – epithelium (Di Girolamo, et al. 2015) Developing trachea and lung (Rock, et al. 2009) |
Skin – Krt14(−/−) does not lead to the ablation of a basal cell cytoskeleton (Krt15 compensation mechanism; Peters et al. 2001) Human mutations in KRT5 and KRT14 cause Epidermolysis bullosa simplex (Peters et al. 2001) |
|
| KRT15 | SG – not reported | SG - No Krt15-deficient SG studies reported |
| Hair follicle – bulge and secondary hair germ (Ito, et al. 2005; Wang, et al., 2011; Morris, et al. 2004) | No Krt15-deficient studies reported | |
| KRT19 | SG – not reported | SG - No Krt19-deficient SG studies reported |
|
Exocrine pancreas, liver – duct cells (Means, et al., 2008) Stomach, intestine (Means, et al., 2008) |
No Krt19-deficient studies reported | |
| LGR4/LGR5/LGR6 | SG – not reported | SG – Lgr5 KO – fusion of tongue to floor of oral cavity, SG phenotype not reported (Morita, et al. 2004) |
|
Ovary (Ng, et al. 2014) Kidney nephron (Barker, et al. 2012) Skin and hair follicle (Jaks, et al. 2008) Intestine (Barker and Cleavers, 2010) Stomach (Barker, et al. 2010) |
Kidney - dilated kidney tubules and ectatic Bowman’s spaces in Lgr4 KO (Kinzel, et al. 2014) Skin – reduced basal cell proliferation and hair follicles in Lgr4 KO (Kinzel, et al. 2014). No effect on epidermal repair in Lgr6 KO (Jiang, et al. 2017) Intestine – loss of stem cells in Lgr4 KO (Kinzel, et al. 2014) and gastrointestinal tract dilation (Morita, et al. 2004) Lgr4 and Lgr5 KO are perinatal lethal (Kinzel, et al. 2014; Morita, et al. 2004) |
|
| P63 | SG – not reported | SG - aplasia in KO (Yang A, et al., 1999) |
|
Prostate (fetal) (Pignon, et al. 2013) Bladder (fetal) (Pignon, et al. 2013) Colorectal epithelium (fetal) (Pignon, et al. 2013) |
Skin – absence of squamous epithelia and derivatives in KO (Yang A, et al., 1999; Senoo, et al. 2007) Limb – truncations in KO (Yang A, et al., 1999) Craniofacial - defects in KO (Yang A, et al., 1999) Mammary and lacrimal glands – absent in KO (Yang A, et al., 1999) |
|
| PAX6 | SG – not reported | SG - abnormal development in the KO (Jaskoll, T. et al., 2002) |
|
Cornea and lens (Lin, et al. 2016) Limbs (fetal) (Li, et al. 2015) |
Eye – impaired retina, lacrimal gland and eye development in the KO (Remez, et al. 2017; Marenkova, et al. 2000) | |
| SOX2 | SG – fetal; acini, ducts (Arnold, et al., 2011; Emmerson et al. 2017), adult; acini only (Arnold, et al., 2011; Emmerson et al. 2018) |
SG – (fetal) reduced epithelial branching in conditional KO (K14CreERT2; Sox2fl/fl; Emmerson et al. 2017) SG – (adult) loss of acini in conditional KO (Sox2CreERT2; Sox2fl/fl and Sox2CreERT2; R26DTA; Emmerson et al. 2018) |
|
Stomach (Arnold, et al., 2011) Cervix (Arnold, et al., 2011) Anus (Arnold, et al., 2011) Testes (Arnold, et al., 2011) Lens (Arnold, et al., 2011) Eosophagus (Arnold, et al., 2011) |
Dermal papilla of hair follicle – no phenotype in conditional KO (K14Cre; Sox2fl/fl; Lesko, et al. 2013) Merkel cells – decreased number in conditional KO (K14Cre; Sox2fl/fl; Lesko, et al. 2013) |
|
| SOX9 | SG – fetal; acini, ducts (Chatzeli, et al. 2017) | SG - reduced branching the KO (Krt14CreERT2; Sox9fl/fl) |
|
Liver (Furuyama, et al. 2011) Exocrine pancreas (Furuyama, et al. 2011; Seymour, et al. 2007) Intestine (duodenum) (Furuyama, et al. 2011) Mammary gland (Malhotra, et al. 2014) Lung (Rockich, et al. 2013; Chang, et al. 2013) Tendon (Soeda, et al. 2010) |
Lacrimal gland – branching defect in conditional KO (Sox9fl/fl; Le-Cre+;
Chen, et al. 2014) Harderian and meibomian glands - reduced acini and loss of epithelia in conditional KO (Sox9fl/fl; Le-Cre+; Chen, et al. 2014) Skin - missing hair in eyelids and facial skin in conditional KO (Sox9fl/fl; Le-Cre+; Chen, et al. 2014) |
|
| SOX10 | SG – not reported | SG - No Sox10-deficient SG studies reported |
| No lineage tracing studies reported |
Lacrimal gland – reduced acini and branching defect in conditional KO (Sox10fl/fl; Le-Cre+;
Chen, et al. 2014) Harderian glands - reduced acini and branching defect in conditional KO (Sox10fl/fl; Le-Cre+; Chen, et al. 2014) |