Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche.
Animals
Cadherins
/ genetics
Cells, Cultured
Epithelial Cells
/ cytology
Hedgehog Proteins
/ genetics
Incisor
/ cytology
Mice, Knockout
Mice, Transgenic
Models, Biological
Patched-1 Receptor
/ genetics
Patched-2 Receptor
/ genetics
Receptors, G-Protein-Coupled
/ genetics
SOXB1 Transcription Factors
/ genetics
Signal Transduction
/ genetics
Stem Cell Niche
Stem Cells
/ cytology
Cervical loop
Hedgehog
Patched
Stem cell niche
Tooth epithelial stem cells
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
06
02
2019
revised:
29
04
2019
accepted:
14
05
2019
pubmed:
31
5
2019
medline:
1
7
2020
entrez:
31
5
2019
Statut:
ppublish
Résumé
Continuous growth of the mouse incisor teeth is due to the life-long maintenance of epithelial stem cells (SCs) in their niche called cervical loop (CL). Several signaling factors regulate SC maintenance and/or their differentiation to achieve organ homeostasis. Previous studies indicated that Hedgehog signaling is crucial for both the maintenance of the SCs in the niche, as well as for their differentiation. How Hedgehog signaling regulates these two opposing cellular behaviors within the confinement of the CL remains elusive. In this study, we used in vitro organ and cell cultures to pharmacologically attenuate Hedgehog signaling. We analyzed expression of various genes expressed in the SC niche to determine the effect of altered Hedgehog signaling on the cellular hierarchy within the niche. These genes include markers of SCs (Sox2 and Lgr5) and transit-amplifying cells (P-cadherin, Sonic Hedgehog, and Yap). Our results show that Hedgehog signaling is a critical survival factor for SCs in the niche, and that the architecture and the diversity of the SC niche are regulated by multiple Hedgehog ligands. We demonstrated the presence of an additional Hedgehog ligand, nerve-derived Desert Hedgehog, secreted in the proximity of the CL. In addition, we provide evidence that Hedgehog receptors Ptch1 and Ptch2 elicit independent responses, which enable multimodal Hedgehog signaling to simultaneously regulate SC maintenance and differentiation. Our study indicates that the cellular hierarchy in the continuously growing incisor is a result of complex interplay of two Hedgehog ligands with functionally distinct Ptch receptors. Stem Cells 2019;37:1238-1248.
Identifiants
pubmed: 31145830
doi: 10.1002/stem.3042
pmc: PMC7859980
mid: NIHMS1660733
doi:
Substances chimiques
Cadherins
0
Hedgehog Proteins
0
Lgr5 protein, mouse
0
Patched-1 Receptor
0
Patched-2 Receptor
0
Receptors, G-Protein-Coupled
0
SOXB1 Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1238-1248Subventions
Organisme : NINDS NIH HHS
ID : R01 NS037956
Pays : United States
Informations de copyright
©AlphaMed Press 2019.
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