{"id":{"repo_id":"oxford-brookes","oai_identifier":"tle:080342b4-d1a3-4d22-8251-6b157d0eaecb:d6bd9758-527a-46cd-bfe2-c433766e8fca:1"},"canonical_url":"https://search.dev.ndltd.org/etd/oxford-brookes/tle:080342b4-d1a3-4d22-8251-6b157d0eaecb:d6bd9758-527a-46cd-bfe2-c433766e8fca:1","repository":{"repo_id":"oxford-brookes","name":"Oxford Brookes University","base_url":"https://radar.brookes.ac.uk/radar/oai"},"display":{"title":"Investigating the evolution and function of Wnt ligands","abstract":"Wnt genes encode secreted glycoproteins which play an important role in development of all animals. Overall, thirteen subfamilies of Wnt ligands are present and all of them can already be found in the most basal metazoans. The importance of this large gene family and its evolutionary conservation intrigued me to analyse Wnts with a variety of different approaches. Starting with a broad evolutionary approach, the losses, conservation and duplication within the Wnt gene repertoire throughout the metazoan phylogeny were studied to understand the underlying evolutionary constrains which were fundamental to create this diverse Wnt landscape. I focussed on elucidating the Wnt gene losses and duplications in arthropods where I found support for the loss of Wnt2 and Wnt4 in all insects, loss of Wnt16 in all insets except Hemiptera and loss of Wnt8 and Wnt9 in Hymenoptera, while Chelicerata, such as spiders and scorpions have lost Wnt10. In horseshoe crabs, spiders and scorpions, duplications of Wnt7 and Wnt11 were observed. Taking some of the results from this broad evolutionary analysis, it would be interesting to understand on a finer scale how the expression or function of Wnt genes is conserved throughout more closely related species. Here, Lepidoptera became of certain interest due to their close relation toits sister groups Diptera and Coleoptera. The expression of Wnts is well known in Drosophila (Diptera) and Tribolium (Coleoptera) but relatively less is understood about Wnt gene expression in butterflies and moths (Lepidoptera). Showing the expression of Wnts in Lepidoptera and being able to compare these results with known patterns from closely related taxa could help to understand if also the function of Wnts could be conserved within phyla. Interestingly, it was possible to show that some Wnts genes (Wnt1, A and 10) have similar expression in all three analysed classes. This hints that in these closer related groups the function of Wnts could be conserved as well and therefore could also be able to influence the evolution of the ligands itself. In the third part of this thesis, the exact function of Wnts was even more narrowed down. For this purpose, Drosophila melanogaster was used and puzzlingly, even in a well-studied model organism such as Drosophila, the function of some of the Wnts is not fully understood. wingless for example is the most studied Wnt gene in Drosophila, while the role during development for Wnt6 and Wnt10 remains unclear. In the following analysis, the focus was on Wnt6 due to its high sequence similarity to wg, close genomic location and overlapping expression. Wnt6 is also highly conserved in all arthropods and additionally part of the conserved Wnt cluster (Wnt1-6-9-10). Hence, the function of Wnt6 during development was studied and also these results were linked to the question of how and why Wnt genes are conserved and why so many Wnt ligands are still present in many species. Previously, a potential role of Wnt6 during maxillary palp development was described which was used as a starting point for the functional analysis. Further, a new Wnt6 knockout line, using CRISPR/Cas9 was generated for comparison to a published knockout line. During the analysis a putative regulatory function of the first exon of Wnt6 was found, which might influence a crucial wg signal during palp development. Wnt6 itself might be involved in regulating the correct growth and pupariation signal during larval development. This analysis also added an additional components, including the regulation of Wnt ligands of the ancestral Wnt cluster to the potential evolutionary mechanisms. Taking all of these results together it was possible to highlight the large diversity of the Wnt landscape in arthropods and indicate clues about the underlying evolutionary mechanisms. Analysing the exact function of Wnt6 also revealed that the genomic location or the clustering of Wnts could play a role in constraining evolution on these genes due to regulatory region within the genes. Overall, this study contributes to increase our understanding of Wnt gene evolution as well as the function and regulation of Wnt ligands.","abstract_html":"Wnt genes encode secreted glycoproteins which play an important role in development of all animals. Overall, thirteen subfamilies of Wnt ligands are present and all of them can already be found in the most basal metazoans. The importance of this large gene family and its evolutionary conservation intrigued me to analyse Wnts with a variety of different approaches. Starting with a broad evolutionary approach, the losses, conservation and duplication within the Wnt gene repertoire throughout the metazoan phylogeny were studied to understand the underlying evolutionary constrains which were fundamental to create this diverse Wnt landscape. I focussed on elucidating the Wnt gene losses and duplications in arthropods where I found support for the loss of Wnt2 and Wnt4 in all insects, loss of Wnt16 in all insets except Hemiptera and loss of Wnt8 and Wnt9 in Hymenoptera, while Chelicerata, such as spiders and scorpions have lost Wnt10. In horseshoe crabs, spiders and scorpions, duplications of Wnt7 and Wnt11 were observed. Taking some of the results from this broad evolutionary analysis, it would be interesting to understand on a finer scale how the expression or function of Wnt genes is conserved throughout more closely related species. Here, Lepidoptera became of certain interest due to their close relation toits sister groups Diptera and Coleoptera. The expression of Wnts is well known in Drosophila (Diptera) and Tribolium (Coleoptera) but relatively less is understood about Wnt gene expression in butterflies and moths (Lepidoptera). Showing the expression of Wnts in Lepidoptera and being able to compare these results with known patterns from closely related taxa could help to understand if also the function of Wnts could be conserved within phyla. Interestingly, it was possible to show that some Wnts genes (Wnt1, A and 10) have similar expression in all three analysed classes. This hints that in these closer related groups the function of Wnts could be conserved as well and therefore could also be able to influence the evolution of the ligands itself. In the third part of this thesis, the exact function of Wnts was even more narrowed down. For this purpose, Drosophila melanogaster was used and puzzlingly, even in a well-studied model organism such as Drosophila, the function of some of the Wnts is not fully understood. wingless for example is the most studied Wnt gene in Drosophila, while the role during development for Wnt6 and Wnt10 remains unclear. In the following analysis, the focus was on Wnt6 due to its high sequence similarity to wg, close genomic location and overlapping expression. Wnt6 is also highly conserved in all arthropods and additionally part of the conserved Wnt cluster (Wnt1-6-9-10). Hence, the function of Wnt6 during development was studied and also these results were linked to the question of how and why Wnt genes are conserved and why so many Wnt ligands are still present in many species. Previously, a potential role of Wnt6 during maxillary palp development was described which was used as a starting point for the functional analysis. Further, a new Wnt6 knockout line, using CRISPR/Cas9 was generated for comparison to a published knockout line. During the analysis a putative regulatory function of the first exon of Wnt6 was found, which might influence a crucial wg signal during palp development. Wnt6 itself might be involved in regulating the correct growth and pupariation signal during larval development. This analysis also added an additional components, including the regulation of Wnt ligands of the ancestral Wnt cluster to the potential evolutionary mechanisms. Taking all of these results together it was possible to highlight the large diversity of the Wnt landscape in arthropods and indicate clues about the underlying evolutionary mechanisms. Analysing the exact function of Wnt6 also revealed that the genomic location or the clustering of Wnts could play a role in constraining evolution on these genes due to regulatory region within the genes. Overall, this study contributes to increase our understanding of Wnt gene evolution as well as the function and regulation of Wnt ligands.","abstract_has_math":false,"creators":["Holzem, Michaela"],"institution":"Oxford Brookes University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["McGregor, Alistair","Santos Nunes, Maria Daniela"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018","date_published":"2018","updated_at":"2026-07-24T03:43:30Z","subjects":[],"languages":["en"],"rights":["All rights reserved"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.24384/dfch-rh04","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Holzem, Michaela","McGregor, Alistair","Santos Nunes, Maria Daniela"]},{"key":"dc:creator","label":"Author","values":["Holzem, Michaela"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018"]},{"key":"dc:publisher","label":"Institution","values":["Oxford Brookes University"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["All rights reserved"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.24384/dfch-rh04","https://radar.brookes.ac.uk/radar/file/080342b4-d1a3-4d22-8251-6b157d0eaecb/1/fulltext.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Wnt genes encode secreted glycoproteins which play an important role in development of all animals. Overall, thirteen subfamilies of Wnt ligands are present and all of them can already be found in the most basal metazoans. The importance of this large gene family and its evolutionary conservation intrigued me to analyse Wnts with a variety of different approaches. Starting with a broad evolutionary approach, the losses, conservation and duplication within the Wnt gene repertoire throughout the metazoan phylogeny were studied to understand the underlying evolutionary constrains which were fundamental to create this diverse Wnt landscape. I focussed on elucidating the Wnt gene losses and duplications in arthropods where I found support for the loss of Wnt2 and Wnt4 in all insects, loss of Wnt16 in all insets except Hemiptera and loss of Wnt8 and Wnt9 in Hymenoptera, while Chelicerata, such as spiders and scorpions have lost Wnt10. In horseshoe crabs, spiders and scorpions, duplications of Wnt7 and Wnt11 were observed. Taking some of the results from this broad evolutionary analysis, it would be interesting to understand on a finer scale how the expression or function of Wnt genes is conserved throughout more closely related species. Here, Lepidoptera became of certain interest due to their close relation toits sister groups Diptera and Coleoptera. The expression of Wnts is well known in Drosophila (Diptera) and Tribolium (Coleoptera) but relatively less is understood about Wnt gene expression in butterflies and moths (Lepidoptera). Showing the expression of Wnts in Lepidoptera and being able to compare these results with known patterns from closely related taxa could help to understand if also the function of Wnts could be conserved within phyla. Interestingly, it was possible to show that some Wnts genes (Wnt1, A and 10) have similar expression in all three analysed classes. This hints that in these closer related groups the function of Wnts could be conserved as well and therefore could also be able to influence the evolution of the ligands itself. In the third part of this thesis, the exact function of Wnts was even more narrowed down. For this purpose, Drosophila melanogaster was used and puzzlingly, even in a well-studied model organism such as Drosophila, the function of some of the Wnts is not fully understood. wingless for example is the most studied Wnt gene in Drosophila, while the role during development for Wnt6 and Wnt10 remains unclear. In the following analysis, the focus was on Wnt6 due to its high sequence similarity to wg, close genomic location and overlapping expression. Wnt6 is also highly conserved in all arthropods and additionally part of the conserved Wnt cluster (Wnt1-6-9-10). Hence, the function of Wnt6 during development was studied and also these results were linked to the question of how and why Wnt genes are conserved and why so many Wnt ligands are still present in many species. Previously, a potential role of Wnt6 during maxillary palp development was described which was used as a starting point for the functional analysis. Further, a new Wnt6 knockout line, using CRISPR/Cas9 was generated for comparison to a published knockout line. During the analysis a putative regulatory function of the first exon of Wnt6 was found, which might influence a crucial wg signal during palp development. Wnt6 itself might be involved in regulating the correct growth and pupariation signal during larval development. This analysis also added an additional components, including the regulation of Wnt ligands of the ancestral Wnt cluster to the potential evolutionary mechanisms. Taking all of these results together it was possible to highlight the large diversity of the Wnt landscape in arthropods and indicate clues about the underlying evolutionary mechanisms. Analysing the exact function of Wnt6 also revealed that the genomic location or the clustering of Wnts could play a role in constraining evolution on these genes due to regulatory region within the genes. Overall, this study contributes to increase our understanding of Wnt gene evolution as well as the function and regulation of Wnt ligands."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Investigating the evolution and function of Wnt ligands"]}]}],"canonical_facts":{"dc:contributor":["Holzem, Michaela","McGregor, Alistair","Santos Nunes, Maria Daniela"],"dc:creator":["Holzem, Michaela"],"dc:date":["2018"],"dc:description":["Wnt genes encode secreted glycoproteins which play an important role in development of all animals. Overall, thirteen subfamilies of Wnt ligands are present and all of them can already be found in the most basal metazoans. The importance of this large gene family and its evolutionary conservation intrigued me to analyse Wnts with a variety of different approaches. Starting with a broad evolutionary approach, the losses, conservation and duplication within the Wnt gene repertoire throughout the metazoan phylogeny were studied to understand the underlying evolutionary constrains which were fundamental to create this diverse Wnt landscape. I focussed on elucidating the Wnt gene losses and duplications in arthropods where I found support for the loss of Wnt2 and Wnt4 in all insects, loss of Wnt16 in all insets except Hemiptera and loss of Wnt8 and Wnt9 in Hymenoptera, while Chelicerata, such as spiders and scorpions have lost Wnt10. In horseshoe crabs, spiders and scorpions, duplications of Wnt7 and Wnt11 were observed. Taking some of the results from this broad evolutionary analysis, it would be interesting to understand on a finer scale how the expression or function of Wnt genes is conserved throughout more closely related species. Here, Lepidoptera became of certain interest due to their close relation toits sister groups Diptera and Coleoptera. The expression of Wnts is well known in Drosophila (Diptera) and Tribolium (Coleoptera) but relatively less is understood about Wnt gene expression in butterflies and moths (Lepidoptera). Showing the expression of Wnts in Lepidoptera and being able to compare these results with known patterns from closely related taxa could help to understand if also the function of Wnts could be conserved within phyla. Interestingly, it was possible to show that some Wnts genes (Wnt1, A and 10) have similar expression in all three analysed classes. This hints that in these closer related groups the function of Wnts could be conserved as well and therefore could also be able to influence the evolution of the ligands itself. In the third part of this thesis, the exact function of Wnts was even more narrowed down. For this purpose, Drosophila melanogaster was used and puzzlingly, even in a well-studied model organism such as Drosophila, the function of some of the Wnts is not fully understood. wingless for example is the most studied Wnt gene in Drosophila, while the role during development for Wnt6 and Wnt10 remains unclear. In the following analysis, the focus was on Wnt6 due to its high sequence similarity to wg, close genomic location and overlapping expression. Wnt6 is also highly conserved in all arthropods and additionally part of the conserved Wnt cluster (Wnt1-6-9-10). Hence, the function of Wnt6 during development was studied and also these results were linked to the question of how and why Wnt genes are conserved and why so many Wnt ligands are still present in many species. Previously, a potential role of Wnt6 during maxillary palp development was described which was used as a starting point for the functional analysis. Further, a new Wnt6 knockout line, using CRISPR/Cas9 was generated for comparison to a published knockout line. During the analysis a putative regulatory function of the first exon of Wnt6 was found, which might influence a crucial wg signal during palp development. Wnt6 itself might be involved in regulating the correct growth and pupariation signal during larval development. This analysis also added an additional components, including the regulation of Wnt ligands of the ancestral Wnt cluster to the potential evolutionary mechanisms. Taking all of these results together it was possible to highlight the large diversity of the Wnt landscape in arthropods and indicate clues about the underlying evolutionary mechanisms. Analysing the exact function of Wnt6 also revealed that the genomic location or the clustering of Wnts could play a role in constraining evolution on these genes due to regulatory region within the genes. Overall, this study contributes to increase our understanding of Wnt gene evolution as well as the function and regulation of Wnt ligands."],"dc:format":["application/pdf"],"dc:identifier":["https://doi.org/10.24384/dfch-rh04","https://radar.brookes.ac.uk/radar/file/080342b4-d1a3-4d22-8251-6b157d0eaecb/1/fulltext.pdf"],"dc:language":["en"],"dc:publisher":["Oxford Brookes University"],"dc:rights":["All rights reserved"],"dc:title":["Investigating the evolution and function of Wnt ligands"],"dc:type":["thesis"]},"updated_at":"2026-07-24T03:43:30Z"}