Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development
<p dir="ltr"><i>WDR11</i>, a gene associated with Kallmann syndrome, is important in reproductive system development but molecular understanding of its action remains incomplete. We previously reported that <i>Wdr11</i>-deficient embryos exhibit defective cili...
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2023
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| _version_ | 1864513507148431360 |
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| author | Jiyoung Lee (41796) |
| author2 | Yeonjoo Kim (14191643) Paris Ataliotis (9260726) Hyung-Goo Kim (728597) Dae-Won Kim (215689) Dorothy C. Bennett (19479832) Nigel A. Brown (19479835) Lawrence C. Layman (13913559) Soo-Hyun Kim (10655) |
| author2_role | author author author author author author author author |
| author_facet | Jiyoung Lee (41796) Yeonjoo Kim (14191643) Paris Ataliotis (9260726) Hyung-Goo Kim (728597) Dae-Won Kim (215689) Dorothy C. Bennett (19479832) Nigel A. Brown (19479835) Lawrence C. Layman (13913559) Soo-Hyun Kim (10655) |
| author_role | author |
| dc.creator.none.fl_str_mv | Jiyoung Lee (41796) Yeonjoo Kim (14191643) Paris Ataliotis (9260726) Hyung-Goo Kim (728597) Dae-Won Kim (215689) Dorothy C. Bennett (19479832) Nigel A. Brown (19479835) Lawrence C. Layman (13913559) Soo-Hyun Kim (10655) |
| dc.date.none.fl_str_mv | 2023-07-29T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41598-023-38017-9 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Coordination_of_canonical_and_noncanonical_Hedgehog_signalling_pathways_mediated_by_WDR11_during_primordial_germ_cell_development/26827813 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics WDR11 Kallmann Syndrome Primordial Germ Cell (PGC) Development Hedgehog (HH) Signalling Canonical and Noncanonical HH Pathways Ciliogenesis |
| dc.title.none.fl_str_mv | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr"><i>WDR11</i>, a gene associated with Kallmann syndrome, is important in reproductive system development but molecular understanding of its action remains incomplete. We previously reported that <i>Wdr11</i>-deficient embryos exhibit defective ciliogenesis and developmental defects associated with Hedgehog (HH) signalling. Here we demonstrate that WDR11 is required for primordial germ cell (PGC) development, regulating canonical and noncanonical HH signalling in parallel. Loss of WDR11 disrupts PGC motility and proliferation driven by the cilia-independent, PTCH2/GAS1-dependent noncanonical HH pathway. WDR11 modulates the growth of somatic cells surrounding PGCs by regulating the cilia-dependent, PTCH1/BOC-dependent canonical HH pathway. We reveal that PTCH1/BOC or PTCH2/GAS1 receptor context dictates SMO localisation inside or outside of cilia, respectively, and loss of WDR11 affects the signalling responses of SMO in both situations. We show that GAS1 is induced by PTCH2-specific HH signalling, which is lost in the absence of WDR11. We also provide evidence supporting a role for WDR11 in ciliogenesis through regulation of anterograde intraflagellar transport potentially via its interaction with IFT20. Since WDR11 is a target of noncanonical SMO signalling, WDR11 represents a novel mechanism by which noncanonical and canonical HH signals communicate and cooperate.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-023-38017-9" target="_blank">https://dx.doi.org/10.1038/s41598-023-38017-9</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_8a58e893f3c7173e08e36f75ce3f39ae |
| identifier_str_mv | 10.1038/s41598-023-38017-9 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26827813 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell developmentJiyoung Lee (41796)Yeonjoo Kim (14191643)Paris Ataliotis (9260726)Hyung-Goo Kim (728597)Dae-Won Kim (215689)Dorothy C. Bennett (19479832)Nigel A. Brown (19479835)Lawrence C. Layman (13913559)Soo-Hyun Kim (10655)Biological sciencesBiochemistry and cell biologyGeneticsWDR11Kallmann SyndromePrimordial Germ Cell (PGC) DevelopmentHedgehog (HH) SignallingCanonical and Noncanonical HH PathwaysCiliogenesis<p dir="ltr"><i>WDR11</i>, a gene associated with Kallmann syndrome, is important in reproductive system development but molecular understanding of its action remains incomplete. We previously reported that <i>Wdr11</i>-deficient embryos exhibit defective ciliogenesis and developmental defects associated with Hedgehog (HH) signalling. Here we demonstrate that WDR11 is required for primordial germ cell (PGC) development, regulating canonical and noncanonical HH signalling in parallel. Loss of WDR11 disrupts PGC motility and proliferation driven by the cilia-independent, PTCH2/GAS1-dependent noncanonical HH pathway. WDR11 modulates the growth of somatic cells surrounding PGCs by regulating the cilia-dependent, PTCH1/BOC-dependent canonical HH pathway. We reveal that PTCH1/BOC or PTCH2/GAS1 receptor context dictates SMO localisation inside or outside of cilia, respectively, and loss of WDR11 affects the signalling responses of SMO in both situations. We show that GAS1 is induced by PTCH2-specific HH signalling, which is lost in the absence of WDR11. We also provide evidence supporting a role for WDR11 in ciliogenesis through regulation of anterograde intraflagellar transport potentially via its interaction with IFT20. Since WDR11 is a target of noncanonical SMO signalling, WDR11 represents a novel mechanism by which noncanonical and canonical HH signals communicate and cooperate.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-023-38017-9" target="_blank">https://dx.doi.org/10.1038/s41598-023-38017-9</a></p>2023-07-29T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-023-38017-9https://figshare.com/articles/journal_contribution/Coordination_of_canonical_and_noncanonical_Hedgehog_signalling_pathways_mediated_by_WDR11_during_primordial_germ_cell_development/26827813CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/268278132023-07-29T09:00:00Z |
| spellingShingle | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development Jiyoung Lee (41796) Biological sciences Biochemistry and cell biology Genetics WDR11 Kallmann Syndrome Primordial Germ Cell (PGC) Development Hedgehog (HH) Signalling Canonical and Noncanonical HH Pathways Ciliogenesis |
| status_str | publishedVersion |
| title | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development |
| title_full | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development |
| title_fullStr | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development |
| title_full_unstemmed | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development |
| title_short | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development |
| title_sort | Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development |
| topic | Biological sciences Biochemistry and cell biology Genetics WDR11 Kallmann Syndrome Primordial Germ Cell (PGC) Development Hedgehog (HH) Signalling Canonical and Noncanonical HH Pathways Ciliogenesis |