The hedgehog co-receptor BOC differentially regulates SHH signaling during craniofacial development
© 2020. Published by The Company of Biologists Ltd..
The Hedgehog (HH) pathway controls multiple aspects of craniofacial development. HH ligands signal through the canonical receptor PTCH1, and three co-receptors: GAS1, CDON and BOC. Together, these co-receptors are required during embryogenesis to mediate proper HH signaling. Here, we investigated the individual and combined contributions of GAS1, CDON and BOC to HH-dependent mammalian craniofacial development. Notably, individual deletion of either Gas1 or Cdon results in variable holoprosencephaly phenotypes in mice, even on a congenic background. In contrast, we find that Boc deletion results in facial widening that correlates with increased HH target gene expression. In addition, Boc deletion in a Gas1 null background partially ameliorates the craniofacial defects observed in Gas1 single mutants; a phenotype that persists over developmental time, resulting in significant improvements to a subset of craniofacial structures. This contrasts with HH-dependent phenotypes in other tissues that significantly worsen following combined deletion of Gas1 and Boc Together, these data indicate that BOC acts as a multi-functional regulator of HH signaling during craniofacial development, alternately promoting or restraining HH pathway activity in a tissue-specific fashion.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:147 |
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| Enthalten in: |
Development (Cambridge, England) - 147(2020), 23 vom: 14. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Echevarría-Andino, Martha L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.01.2021 Date Revised 15.08.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1242/dev.189076 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316296619 |
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| 100 | 1 | |a Echevarría-Andino, Martha L |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The hedgehog co-receptor BOC differentially regulates SHH signaling during craniofacial development |
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| 500 | |a Date Revised 15.08.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020. Published by The Company of Biologists Ltd. | ||
| 520 | |a The Hedgehog (HH) pathway controls multiple aspects of craniofacial development. HH ligands signal through the canonical receptor PTCH1, and three co-receptors: GAS1, CDON and BOC. Together, these co-receptors are required during embryogenesis to mediate proper HH signaling. Here, we investigated the individual and combined contributions of GAS1, CDON and BOC to HH-dependent mammalian craniofacial development. Notably, individual deletion of either Gas1 or Cdon results in variable holoprosencephaly phenotypes in mice, even on a congenic background. In contrast, we find that Boc deletion results in facial widening that correlates with increased HH target gene expression. In addition, Boc deletion in a Gas1 null background partially ameliorates the craniofacial defects observed in Gas1 single mutants; a phenotype that persists over developmental time, resulting in significant improvements to a subset of craniofacial structures. This contrasts with HH-dependent phenotypes in other tissues that significantly worsen following combined deletion of Gas1 and Boc Together, these data indicate that BOC acts as a multi-functional regulator of HH signaling during craniofacial development, alternately promoting or restraining HH pathway activity in a tissue-specific fashion | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a BOC | |
| 650 | 4 | |a CDON | |
| 650 | 4 | |a Craniofacial development | |
| 650 | 4 | |a GAS1 | |
| 650 | 4 | |a Hedgehog | |
| 650 | 4 | |a Holoprosencephaly | |
| 650 | 4 | |a Mouse | |
| 650 | 7 | |a Boc protein, mouse |2 NLM | |
| 650 | 7 | |a Cdon protein, mouse |2 NLM | |
| 650 | 7 | |a Cell Adhesion Molecules |2 NLM | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 650 | 7 | |a GPI-Linked Proteins |2 NLM | |
| 650 | 7 | |a Gas1 protein, mouse |2 NLM | |
| 650 | 7 | |a Hedgehog Proteins |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Patched-1 Receptor |2 NLM | |
| 650 | 7 | |a Ptch1 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 700 | 1 | |a Allen, Benjamin L |e verfasserin |4 aut | |
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