{"id":{"repo_id":"freiburg-diss","oai_identifier":"oai:freidok.uni-freiburg.de:1769"},"canonical_url":"https://search.dev.ndltd.org/etd/freiburg-diss/oai:freidok.uni-freiburg.de:1769","repository":{"repo_id":"freiburg-diss","name":"University of Freiburg","base_url":"https://freidok.uni-freiburg.de/oai/oai2.php"},"display":{"title":"Die Rolle von cDermo-1 und cTwist im Vogelembryo","abstract":"The aim of this work was to study the regulation and function of the bHLH transcription factors cTwist and cDermo-1. The results obtained may be summarized as follows. <br> <br>1) The induction of cTwist in the paraxial mesoderm of the chick embryo is dependant upon signals emanating from the axial organs. Barrier insertion results in loss of this expression. This effect was rescued by combination of Shh and FGF-8. Furthermore, we could show that the maintenance of the cTwist expression was independent of the inducing signals. Finally BMP-2 is able to downregulate cTwist at early stages while it leads to an upregulation of cTwist later on in development. This indicates an anti-apoptotic function for cTwist in vivo. <br> <br>2) The dermis of the back develops from two separate progenitor populations of the dermomyotome differently regulated by signals from the surrounding structures. The dorsomedial population emanates from the medial lip, where it expresses Wnt-11 and migrates towards the dermis directly overlying the neural tube. This population may be promoted by a Wnt-1 signal from the neural tube as well as an FGF-4 signal, while it is inhibited by Noggin. The dorsolateral progenitor cells deepithelialise out of the central dermomyotome where they express En-1, which is downregulated by BMP, promoting the dermis development in the area directly overlying the somites. These cells also express Wnt-11 and are additionally promoted by an FGF signal. As opposed to the dorsomedial cells however, they are inhibited by Wnt-1. Finally, to support our hypothesis that a downregulation of En-1 in the dorsolateral progenitor population is necessary for dermal differentiation, we retrovirally overexpressed En-1 and showed that this inhibited both dermis and skin appendage development. <br> <br>3) In the development of dermis and skin appendages, we could show that cDermo-1 is essential to induce differentiation of dermal progenitors. Retroviral overexpression of cDermo-1 in the back as well as the limb bud of the chick embryo resulted in the formation of ectopic dermis and skin appendages with respect to the position of the dermis within the embryo. This shows that cDermo-1 is a universal inducer of skin appendages and does not carry a positional information determining the nature of the appendage formed. To further confirm the inducing function of cDermo-1 in dermis development, we downregulated it at earliest developmental stages in both progenitor populations of the back with the help of an ectopic Wnt-4 signal. After reincubation, an inhibition of dermis development and an absence of skin appendages became evident. Finally, we showed that the determining function of cDermo-1 occurred in cells that have already deepithelialised from the somite, and that cDermo-1 had no influence on the process of somite patterning. <br> <br>The aim of future experiments will be to determine the nature of cDermo-1 targets as well as the role played by cell migration in the process of dermal development.","abstract_html":"The aim of this work was to study the regulation and function of the bHLH transcription factors cTwist and cDermo-1. The results obtained may be summarized as follows. &lt;br&gt; &lt;br&gt;1) The induction of cTwist in the paraxial mesoderm of the chick embryo is dependant upon signals emanating from the axial organs. Barrier insertion results in loss of this expression. This effect was rescued by combination of Shh and FGF-8. Furthermore, we could show that the maintenance of the cTwist expression was independent of the inducing signals. Finally BMP-2 is able to downregulate cTwist at early stages while it leads to an upregulation of cTwist later on in development. This indicates an anti-apoptotic function for cTwist in vivo. &lt;br&gt; &lt;br&gt;2) The dermis of the back develops from two separate progenitor populations of the dermomyotome differently regulated by signals from the surrounding structures. The dorsomedial population emanates from the medial lip, where it expresses Wnt-11 and migrates towards the dermis directly overlying the neural tube. This population may be promoted by a Wnt-1 signal from the neural tube as well as an FGF-4 signal, while it is inhibited by Noggin. The dorsolateral progenitor cells deepithelialise out of the central dermomyotome where they express En-1, which is downregulated by BMP, promoting the dermis development in the area directly overlying the somites. These cells also express Wnt-11 and are additionally promoted by an FGF signal. As opposed to the dorsomedial cells however, they are inhibited by Wnt-1. Finally, to support our hypothesis that a downregulation of En-1 in the dorsolateral progenitor population is necessary for dermal differentiation, we retrovirally overexpressed En-1 and showed that this inhibited both dermis and skin appendage development. &lt;br&gt; &lt;br&gt;3) In the development of dermis and skin appendages, we could show that cDermo-1 is essential to induce differentiation of dermal progenitors. Retroviral overexpression of cDermo-1 in the back as well as the limb bud of the chick embryo resulted in the formation of ectopic dermis and skin appendages with respect to the position of the dermis within the embryo. This shows that cDermo-1 is a universal inducer of skin appendages and does not carry a positional information determining the nature of the appendage formed. To further confirm the inducing function of cDermo-1 in dermis development, we downregulated it at earliest developmental stages in both progenitor populations of the back with the help of an ectopic Wnt-4 signal. After reincubation, an inhibition of dermis development and an absence of skin appendages became evident. Finally, we showed that the determining function of cDermo-1 occurred in cells that have already deepithelialised from the somite, and that cDermo-1 had no influence on the process of somite patterning. &lt;br&gt; &lt;br&gt;The aim of future experiments will be to determine the nature of cDermo-1 targets as well as the role played by cell migration in the process of dermal development.","abstract_has_math":false,"creators":["Hornik, Christoph Paul Vincent"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Brand-Saberi, Beate"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T02:22:28Z","subjects":["Dermis"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://freidok.uni-freiburg.de/data/1769","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Brand-Saberi, Beate"]},{"key":"dc:creator","label":"Author","values":["Hornik, Christoph Paul Vincent"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:type","label":"Dc Type","values":["DoctoralThesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Dermis"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The aim of this work was to study the regulation and function of the bHLH transcription factors cTwist and cDermo-1. The results obtained may be summarized as follows. <br> <br>1) The induction of cTwist in the paraxial mesoderm of the chick embryo is dependant upon signals emanating from the axial organs. Barrier insertion results in loss of this expression. This effect was rescued by combination of Shh and FGF-8. Furthermore, we could show that the maintenance of the cTwist expression was independent of the inducing signals. Finally BMP-2 is able to downregulate cTwist at early stages while it leads to an upregulation of cTwist later on in development. This indicates an anti-apoptotic function for cTwist in vivo. <br> <br>2) The dermis of the back develops from two separate progenitor populations of the dermomyotome differently regulated by signals from the surrounding structures. The dorsomedial population emanates from the medial lip, where it expresses Wnt-11 and migrates towards the dermis directly overlying the neural tube. This population may be promoted by a Wnt-1 signal from the neural tube as well as an FGF-4 signal, while it is inhibited by Noggin. The dorsolateral progenitor cells deepithelialise out of the central dermomyotome where they express En-1, which is downregulated by BMP, promoting the dermis development in the area directly overlying the somites. These cells also express Wnt-11 and are additionally promoted by an FGF signal. As opposed to the dorsomedial cells however, they are inhibited by Wnt-1. Finally, to support our hypothesis that a downregulation of En-1 in the dorsolateral progenitor population is necessary for dermal differentiation, we retrovirally overexpressed En-1 and showed that this inhibited both dermis and skin appendage development. <br> <br>3) In the development of dermis and skin appendages, we could show that cDermo-1 is essential to induce differentiation of dermal progenitors. Retroviral overexpression of cDermo-1 in the back as well as the limb bud of the chick embryo resulted in the formation of ectopic dermis and skin appendages with respect to the position of the dermis within the embryo. This shows that cDermo-1 is a universal inducer of skin appendages and does not carry a positional information determining the nature of the appendage formed. To further confirm the inducing function of cDermo-1 in dermis development, we downregulated it at earliest developmental stages in both progenitor populations of the back with the help of an ectopic Wnt-4 signal. After reincubation, an inhibition of dermis development and an absence of skin appendages became evident. Finally, we showed that the determining function of cDermo-1 occurred in cells that have already deepithelialised from the somite, and that cDermo-1 had no influence on the process of somite patterning. <br> <br>The aim of future experiments will be to determine the nature of cDermo-1 targets as well as the role played by cell migration in the process of dermal development.","Ziel dieser Arbeit war es, Regulation und Funktion der bHLH Transkriptionsfaktoren cTwist und cDermo-1 zu untersuchen. Die erhaltenen Ergebnisse lassen sich wie folgt zusammenfassen: <br> <br>1) Die cTwist Expression im paraxialen Mesoderm des Hühnerembryos wird von <br>Signalen der Axialorgane induziert. Abschirmungsexperimente erlaubten, dieses Signal als eine Kombination von Shh und FGF-8 zu identifizieren. Des weiteren konnte gezeigt werden, dass die Erhaltung der cTwist Expression unabhängig von diesen Signalen erfolgt. Zuletzt war es möglich, durch BMP-2 Applikation in frühen Stadien die Expression von cTwist zu inhibieren. In späteren Stadien führte das BMP-2 Signal dann zu einer Hochregulierung von cTwist, die mit dem Wechsel der BMP Funktion von einem apoptotischen zu einem proliferierenden Signal korrelierte, und damit eine mögliche anti-apoptotische Funktion von cTwist in vivo andeutete. <br> <br>2) Die Dermis des Rückens entwickelt sich aus zwei unabhängigen Vorläuferpopulationen des Dermomyotoms. Die dorsomediale Population stammt aus der medialen Lippe und migriert in das über dem Neuralrohr gelegene Areal. Sie wird durch Wnt-1 stimuliert, während sie durch Noggin gehemmt wird. Die dorsolateralen Vorläuferzellen deepithelialisieren aus dem zentralen, En-1 positiven Dermomyotom. Diese Zellen werden durch ein BMP Signal stimuliert, welches En-1 runterreguliert. Mediale und laterale Dermisvorläuferzellen exprimieren Wnt-11 und werden des weiteren durch ein FGF-4 Signal stimuliert. Wnt-1 inhibiert dagegen die Dermisentwicklung der lateralen Vorläuferpopulation. Wir konnten mit Hilfe eines retroviralen Überexpressionsvektors den negativen Effekt von En-1 auf die Entwicklung der dorsolateralen Dermis und der Hautanhangsgebilde demonstrieren. <br> <br>3) cDermo-1 ist das essentielle Signal in der Entwicklung von Haut und Hautanhangsgebilden. Dies konnten wir mit Hilfe retroviraler Überexpression im Rücken und in den Extremitätenknospen des Hühnerembryos zeigen. Bemerkenswerterweise war die Identität der induzierten Hautanhangsgebilde abhängig von der Lokalisation der cDermo-1 Überexpression. Dies zeigt dass, cDermo-1 positionsübergreifend wirkt. Um die essentielle Funktion von cDermo-1 in der Dermisentwicklung zu unterstreichen, haben wir in frühen Stadien die cDermo-1 Expression mittels Wnt-4 Applikation inhibiert und nach längeren Reinkubationszeiten das Fehlen von Dermis und Federknospen festgestellt. Schließlich konnten wir zeigen, dass cDermo-1 Dermisentwicklung in Zellen induziert, die bereits den epithelialen Somiten verlassen haben, und keinen Einfluss auf dessen Kompartimentierung hat. <br> <br>Weitere Experimente werden notwendig sein, um die Zielmoleküle des cDermo-1 Signals zu identifizieren und die Rolle der Zellmigration im Prozess der Dermisentwicklung zu beurteilen."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Die Rolle von cDermo-1 und cTwist im Vogelembryo","The role of cDermo-1 and cTwist in the avian embryo"]}]}],"canonical_facts":{"dc:contributor":["Brand-Saberi, Beate"],"dc:creator":["Hornik, Christoph Paul Vincent"],"dc:description.abstract":["The aim of this work was to study the regulation and function of the bHLH transcription factors cTwist and cDermo-1. The results obtained may be summarized as follows. <br> <br>1) The induction of cTwist in the paraxial mesoderm of the chick embryo is dependant upon signals emanating from the axial organs. Barrier insertion results in loss of this expression. This effect was rescued by combination of Shh and FGF-8. Furthermore, we could show that the maintenance of the cTwist expression was independent of the inducing signals. Finally BMP-2 is able to downregulate cTwist at early stages while it leads to an upregulation of cTwist later on in development. This indicates an anti-apoptotic function for cTwist in vivo. <br> <br>2) The dermis of the back develops from two separate progenitor populations of the dermomyotome differently regulated by signals from the surrounding structures. The dorsomedial population emanates from the medial lip, where it expresses Wnt-11 and migrates towards the dermis directly overlying the neural tube. This population may be promoted by a Wnt-1 signal from the neural tube as well as an FGF-4 signal, while it is inhibited by Noggin. The dorsolateral progenitor cells deepithelialise out of the central dermomyotome where they express En-1, which is downregulated by BMP, promoting the dermis development in the area directly overlying the somites. These cells also express Wnt-11 and are additionally promoted by an FGF signal. As opposed to the dorsomedial cells however, they are inhibited by Wnt-1. Finally, to support our hypothesis that a downregulation of En-1 in the dorsolateral progenitor population is necessary for dermal differentiation, we retrovirally overexpressed En-1 and showed that this inhibited both dermis and skin appendage development. <br> <br>3) In the development of dermis and skin appendages, we could show that cDermo-1 is essential to induce differentiation of dermal progenitors. Retroviral overexpression of cDermo-1 in the back as well as the limb bud of the chick embryo resulted in the formation of ectopic dermis and skin appendages with respect to the position of the dermis within the embryo. This shows that cDermo-1 is a universal inducer of skin appendages and does not carry a positional information determining the nature of the appendage formed. To further confirm the inducing function of cDermo-1 in dermis development, we downregulated it at earliest developmental stages in both progenitor populations of the back with the help of an ectopic Wnt-4 signal. After reincubation, an inhibition of dermis development and an absence of skin appendages became evident. Finally, we showed that the determining function of cDermo-1 occurred in cells that have already deepithelialised from the somite, and that cDermo-1 had no influence on the process of somite patterning. <br> <br>The aim of future experiments will be to determine the nature of cDermo-1 targets as well as the role played by cell migration in the process of dermal development.","Ziel dieser Arbeit war es, Regulation und Funktion der bHLH Transkriptionsfaktoren cTwist und cDermo-1 zu untersuchen. Die erhaltenen Ergebnisse lassen sich wie folgt zusammenfassen: <br> <br>1) Die cTwist Expression im paraxialen Mesoderm des Hühnerembryos wird von <br>Signalen der Axialorgane induziert. Abschirmungsexperimente erlaubten, dieses Signal als eine Kombination von Shh und FGF-8 zu identifizieren. Des weiteren konnte gezeigt werden, dass die Erhaltung der cTwist Expression unabhängig von diesen Signalen erfolgt. Zuletzt war es möglich, durch BMP-2 Applikation in frühen Stadien die Expression von cTwist zu inhibieren. In späteren Stadien führte das BMP-2 Signal dann zu einer Hochregulierung von cTwist, die mit dem Wechsel der BMP Funktion von einem apoptotischen zu einem proliferierenden Signal korrelierte, und damit eine mögliche anti-apoptotische Funktion von cTwist in vivo andeutete. <br> <br>2) Die Dermis des Rückens entwickelt sich aus zwei unabhängigen Vorläuferpopulationen des Dermomyotoms. Die dorsomediale Population stammt aus der medialen Lippe und migriert in das über dem Neuralrohr gelegene Areal. Sie wird durch Wnt-1 stimuliert, während sie durch Noggin gehemmt wird. Die dorsolateralen Vorläuferzellen deepithelialisieren aus dem zentralen, En-1 positiven Dermomyotom. Diese Zellen werden durch ein BMP Signal stimuliert, welches En-1 runterreguliert. Mediale und laterale Dermisvorläuferzellen exprimieren Wnt-11 und werden des weiteren durch ein FGF-4 Signal stimuliert. Wnt-1 inhibiert dagegen die Dermisentwicklung der lateralen Vorläuferpopulation. Wir konnten mit Hilfe eines retroviralen Überexpressionsvektors den negativen Effekt von En-1 auf die Entwicklung der dorsolateralen Dermis und der Hautanhangsgebilde demonstrieren. <br> <br>3) cDermo-1 ist das essentielle Signal in der Entwicklung von Haut und Hautanhangsgebilden. Dies konnten wir mit Hilfe retroviraler Überexpression im Rücken und in den Extremitätenknospen des Hühnerembryos zeigen. Bemerkenswerterweise war die Identität der induzierten Hautanhangsgebilde abhängig von der Lokalisation der cDermo-1 Überexpression. Dies zeigt dass, cDermo-1 positionsübergreifend wirkt. Um die essentielle Funktion von cDermo-1 in der Dermisentwicklung zu unterstreichen, haben wir in frühen Stadien die cDermo-1 Expression mittels Wnt-4 Applikation inhibiert und nach längeren Reinkubationszeiten das Fehlen von Dermis und Federknospen festgestellt. Schließlich konnten wir zeigen, dass cDermo-1 Dermisentwicklung in Zellen induziert, die bereits den epithelialen Somiten verlassen haben, und keinen Einfluss auf dessen Kompartimentierung hat. <br> <br>Weitere Experimente werden notwendig sein, um die Zielmoleküle des cDermo-1 Signals zu identifizieren und die Rolle der Zellmigration im Prozess der Dermisentwicklung zu beurteilen."],"dc:format.medium":["application/pdf"],"dc:subject":["Dermis"],"dc:title":["Die Rolle von cDermo-1 und cTwist im Vogelembryo","The role of cDermo-1 and cTwist in the avian embryo"],"dc:type":["DoctoralThesis"]},"updated_at":"2026-07-24T02:22:28Z"}