Table 1. Genes Implicated in Salivary Gland (SG) Morphogenesis with Their Currently Understood Roles and Interactions.
| Process: Secretory cell invagination | ||
|---|---|---|
| MOLECULE | ROLE | |
| Fkh | Transcription factor Regulates expression of ≈60% of SG genes Maintains SG viability (with Sage and Sens) Mediates invagination |
|
| Fog | Ligand for GPCR Mist in mesoderm Coordinates invagination |
|
| Rho1 | GTPase Increases Crb levels Maintains Crb, aPKC, and Stardust apical localization |
|
| Crb | Apical membrane protein Establishes and maintains apical/basal polarity Along with aPKC, prevents Rok accumulation and Myoll cable formation in SG |
|
| aPKC | Along with Crb, negatively regulates Rok and Myoll | |
| Rok | Rho kinase Induces cell-shape changes and apical constriction Positive regulator of Myoll |
|
| RhoGEF2 | Rho guanine nucleotide exchange Factor Regulates apical constriction via Sqh localization |
|
| Sqh | Myosin regulatory light chain Creates intracellular myosin network |
|
| RhoGAP88C | Basolaterally localized GTPase activating protein Coordinates invagination |
|
| 18-Wheeler | Toll-like receptor Component of Rho pathway Coordinates invagination |
|
| Tec29/Btk29A | Non-receptor tyrosine kinase Affects F- and G- actin dynamics Coordinates invagination and migration |
|
| Gyc76C | Guanylyl cyclase Upstream of DG1 Regulates Talin and laminin localization |
|
| DG1 | cGMP-dependent kinase 1 Downstream of Gyc76C Regulates Talin and laminin localization |
|
| Process: Tube elongation via cell elongation | ||
| MOLECULE | ROLE | |
| Hkb | Transcription factor Upstream of Klar, Crb Mediates apical expansion |
|
| Klar | Mediates apical membrane delivery via vesicle transport | |
| Crb | Transmembrane protein Mediates apical membrane expansion |
|
| Rib | Transcription factor Upstream of Crb Regulates moesin activity (indirect) |
|
| Lolal | Mediates nuclear localization of Rib in the SG (and other ectoderm) | |
| Moesin | ERM family member; actin linker Increases apical stiffness when phosphorylated |
|
| Cdc42 | Rho GTPase; activates Pakl | |
| Pakl | Serine-threonine kinase Regulates lateral E-Cad endocytosis through Merlin, Dynamin, and Rab5 |
|
| E-Cadherin | Cell-cell adhesion Mediates cell shape changes in the SG [e.g. expansion along the apical P/D axis] |
|
| Process: Tube elongation via cell rearrangement | ||
| MOLECULE | ROLE | |
| Racl | Rho GTPase; regulates junctional E-Cad turnover | |
| E-Cadherin | Regulates cell-cell adhesion [too little, cells disperse; too much, cells are unable to rearrange properly] | |
| Gonl | Apically secreted metalloprotease Influences apical membrane release from ECM and consequent cell rearrangements Genetically interacts with Cad99C |
|
| Cad99C | Apically secreted protocadherin Influences apical membrane release from ECM and consequent cell rearrangements |
|