Essential role for ligand-dependent feedback antagonism of vertebrate hedgehog signaling by PTCH1, PTCH2 and HHIP1 during neural patterning
Hedgehog (HH) signaling is essential for vertebrate and invertebrate embryogenesis. In Drosophila, feedback upregulation of the HH receptor Patched (PTC; PTCH in vertebrates), is required to restrict HH signaling during development. By contrast, PTCH1 upregulation is dispensable for early HH-dependent patterning in mice. Unique to vertebrates are two additional HH-binding antagonists that are induced by HH signaling, HHIP1 and the PTCH1 homologue PTCH2. Although HHIP1 functions semi-redundantly with PTCH1 to restrict HH signaling in the developing nervous system, a role for PTCH2 remains unresolved. Data presented here define a novel role for PTCH2 as a ciliary localized HH pathway antagonist. While PTCH2 is dispensable for normal ventral neural patterning, combined removal of PTCH2- and PTCH1-feedback antagonism produces a significant expansion of HH-dependent ventral neural progenitors. Strikingly, complete loss of PTCH2-, HHIP1- and PTCH1-feedback inhibition results in ectopic specification of ventral cell fates throughout the neural tube, reflecting constitutive HH pathway activation. Overall, these data reveal an essential role for ligand-dependent feedback inhibition of vertebrate HH signaling governed collectively by PTCH1, PTCH2 and HHIP1.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:140 |
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| Enthalten in: |
Development (Cambridge, England) - 140(2013), 16 vom: 18. Aug., Seite 3423-34 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Holtz, Alexander M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.10.2013 Date Revised 21.10.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1242/dev.095083 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM229599869 |
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| 100 | 1 | |a Holtz, Alexander M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Essential role for ligand-dependent feedback antagonism of vertebrate hedgehog signaling by PTCH1, PTCH2 and HHIP1 during neural patterning |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 18.10.2013 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Hedgehog (HH) signaling is essential for vertebrate and invertebrate embryogenesis. In Drosophila, feedback upregulation of the HH receptor Patched (PTC; PTCH in vertebrates), is required to restrict HH signaling during development. By contrast, PTCH1 upregulation is dispensable for early HH-dependent patterning in mice. Unique to vertebrates are two additional HH-binding antagonists that are induced by HH signaling, HHIP1 and the PTCH1 homologue PTCH2. Although HHIP1 functions semi-redundantly with PTCH1 to restrict HH signaling in the developing nervous system, a role for PTCH2 remains unresolved. Data presented here define a novel role for PTCH2 as a ciliary localized HH pathway antagonist. While PTCH2 is dispensable for normal ventral neural patterning, combined removal of PTCH2- and PTCH1-feedback antagonism produces a significant expansion of HH-dependent ventral neural progenitors. Strikingly, complete loss of PTCH2-, HHIP1- and PTCH1-feedback inhibition results in ectopic specification of ventral cell fates throughout the neural tube, reflecting constitutive HH pathway activation. Overall, these data reveal an essential role for ligand-dependent feedback inhibition of vertebrate HH signaling governed collectively by PTCH1, PTCH2 and HHIP1 | ||
| 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 Hedgehog | |
| 650 | 4 | |a Negative feedback | |
| 650 | 4 | |a Neural tube | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Hhip protein, mouse |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Membrane Glycoproteins |2 NLM | |
| 650 | 7 | |a Patched Receptors |2 NLM | |
| 650 | 7 | |a Patched-1 Receptor |2 NLM | |
| 650 | 7 | |a Patched-2 Receptor |2 NLM | |
| 650 | 7 | |a Ptch1 protein, mouse |2 NLM | |
| 650 | 7 | |a Ptch2 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 700 | 1 | |a Peterson, Kevin A |e verfasserin |4 aut | |
| 700 | 1 | |a Nishi, Yuichi |e verfasserin |4 aut | |
| 700 | 1 | |a Morin, Steves |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jane Y |e verfasserin |4 aut | |
| 700 | 1 | |a Charron, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a McMahon, Andrew P |e verfasserin |4 aut | |
| 700 | 1 | |a Allen, Benjamin L |e verfasserin |4 aut | |
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