{"id":{"repo_id":"freiburg-diss","oai_identifier":"oai:freidok.uni-freiburg.de:1762"},"canonical_url":"https://search.dev.ndltd.org/etd/freiburg-diss/oai:freidok.uni-freiburg.de:1762","repository":{"repo_id":"freiburg-diss","name":"University of Freiburg","base_url":"https://freidok.uni-freiburg.de/oai/oai2.php"},"display":{"title":"Detailed analysis of Lmx1b expression in multiple organs and its role in dorso-ventral patterning with emphasis on myogenic precursor cells","abstract":"Lmx1b belongs to a family of LIM homeodomain transcription factors expressed in multiple organs. Targeted disruption of Lmx1b results in ventralization of the limbs, skeletal, brain, kidney and ocular defects which resembles the corresponding human Nail-Patella Syndrome (NPS) (Chen et al. 1998a). The generation of transgenic mice carrying a LacZ reporter gene under the control of the endogenous Lmx1b locus allowed detailed analysis of Lmx1b expression. This study provides novel insights in the expression pattern, determines precisely Lmx1b-positive cell types in tissues, and describes for the first time expression in organs. It was demonstrated that Lmx1b expression is present throughout all stages of mammary gland development and restricted to luminal epithelial cells. Mice targeted for Lmx1b lack mammary glands. These findings indicate that Lmx1b plays a pivotal role in mammary gland development. Indeed, female patients with NPS display poor breast development (Sweeney et al. 2003). It is shown that Lmx1b expression is restricted to podocytes in the kidney, indicating the involvement of Lmx1b in nephropathy of NPS patients. No expression was detected in heart, liver and spleen. Lmx1b is involved in pattern formation of the limb and exhibits expression throughout all stages of embryonic development restricted to the dorsal limb mesenchyme. Hereby, Lmx1b expression marks a sharp boundary towards the ventral part of the limb. It is shown that dorsal Lmx1b-positive cells do not sort out from ventral Lmx1b-negative cells. This suggests that the maintenance of the boundary is not triggered by differential cell adhesion in the whole limb, maybe only at the boundary itself. <br>Moreover, interspecific grafting experiments using quail-chick chimeras showed that migrating cells have restricted movement within the dorsal or ventral compartment they attain during transplantation. These findings indicate that migrating cells respect the boundary between the dorsal and ventral compartment and no exchange occurs. Interestingly, although Lmx1b is known as a marker for the dorsal limb mesenchyme, myogenic precursor cells invading the dorsal part of the limb are shown to be devoid of expression. It is also assumed that differentiated muscle lacks Lmx1b expression. In all, this study extends the understanding of limb pattern formation and reveals novel findings concerning proximo-distal differences and migratory pathways. The discovery of Lmx1b expression in organs and its detailed description forms an important basis for further investigations to finally understand and treat human NPS.","abstract_html":"Lmx1b belongs to a family of LIM homeodomain transcription factors expressed in multiple organs. Targeted disruption of Lmx1b results in ventralization of the limbs, skeletal, brain, kidney and ocular defects which resembles the corresponding human Nail-Patella Syndrome (NPS) (Chen et al. 1998a). The generation of transgenic mice carrying a LacZ reporter gene under the control of the endogenous Lmx1b locus allowed detailed analysis of Lmx1b expression. This study provides novel insights in the expression pattern, determines precisely Lmx1b-positive cell types in tissues, and describes for the first time expression in organs. It was demonstrated that Lmx1b expression is present throughout all stages of mammary gland development and restricted to luminal epithelial cells. Mice targeted for Lmx1b lack mammary glands. These findings indicate that Lmx1b plays a pivotal role in mammary gland development. Indeed, female patients with NPS display poor breast development (Sweeney et al. 2003). It is shown that Lmx1b expression is restricted to podocytes in the kidney, indicating the involvement of Lmx1b in nephropathy of NPS patients. No expression was detected in heart, liver and spleen. Lmx1b is involved in pattern formation of the limb and exhibits expression throughout all stages of embryonic development restricted to the dorsal limb mesenchyme. Hereby, Lmx1b expression marks a sharp boundary towards the ventral part of the limb. It is shown that dorsal Lmx1b-positive cells do not sort out from ventral Lmx1b-negative cells. This suggests that the maintenance of the boundary is not triggered by differential cell adhesion in the whole limb, maybe only at the boundary itself. &lt;br&gt;Moreover, interspecific grafting experiments using quail-chick chimeras showed that migrating cells have restricted movement within the dorsal or ventral compartment they attain during transplantation. These findings indicate that migrating cells respect the boundary between the dorsal and ventral compartment and no exchange occurs. Interestingly, although Lmx1b is known as a marker for the dorsal limb mesenchyme, myogenic precursor cells invading the dorsal part of the limb are shown to be devoid of expression. It is also assumed that differentiated muscle lacks Lmx1b expression. In all, this study extends the understanding of limb pattern formation and reveals novel findings concerning proximo-distal differences and migratory pathways. The discovery of Lmx1b expression in organs and its detailed description forms an important basis for further investigations to finally understand and treat human NPS.","abstract_has_math":false,"creators":["Schweizer, Heiko"],"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":["Extremitäten","Brustdrüsen","Reportergen","Lbx1","Muskelvorläuferzellen","Muskelentwicklung","Lmx1b","cell migration","Nail-Patella-Syndrome","mammary gland development"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://freidok.uni-freiburg.de/data/1762","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":["Schweizer, Heiko"]}]},{"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":["Extremitäten","Brustdrüsen","Reportergen","Lbx1","Muskelvorläuferzellen","Muskelentwicklung","Lmx1b","cell migration","Nail-Patella-Syndrome","mammary gland development"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Lmx1b belongs to a family of LIM homeodomain transcription factors expressed in multiple organs. Targeted disruption of Lmx1b results in ventralization of the limbs, skeletal, brain, kidney and ocular defects which resembles the corresponding human Nail-Patella Syndrome (NPS) (Chen et al. 1998a). The generation of transgenic mice carrying a LacZ reporter gene under the control of the endogenous Lmx1b locus allowed detailed analysis of Lmx1b expression. This study provides novel insights in the expression pattern, determines precisely Lmx1b-positive cell types in tissues, and describes for the first time expression in organs. It was demonstrated that Lmx1b expression is present throughout all stages of mammary gland development and restricted to luminal epithelial cells. Mice targeted for Lmx1b lack mammary glands. These findings indicate that Lmx1b plays a pivotal role in mammary gland development. Indeed, female patients with NPS display poor breast development (Sweeney et al. 2003). It is shown that Lmx1b expression is restricted to podocytes in the kidney, indicating the involvement of Lmx1b in nephropathy of NPS patients. No expression was detected in heart, liver and spleen. Lmx1b is involved in pattern formation of the limb and exhibits expression throughout all stages of embryonic development restricted to the dorsal limb mesenchyme. Hereby, Lmx1b expression marks a sharp boundary towards the ventral part of the limb. It is shown that dorsal Lmx1b-positive cells do not sort out from ventral Lmx1b-negative cells. This suggests that the maintenance of the boundary is not triggered by differential cell adhesion in the whole limb, maybe only at the boundary itself. <br>Moreover, interspecific grafting experiments using quail-chick chimeras showed that migrating cells have restricted movement within the dorsal or ventral compartment they attain during transplantation. These findings indicate that migrating cells respect the boundary between the dorsal and ventral compartment and no exchange occurs. Interestingly, although Lmx1b is known as a marker for the dorsal limb mesenchyme, myogenic precursor cells invading the dorsal part of the limb are shown to be devoid of expression. It is also assumed that differentiated muscle lacks Lmx1b expression. In all, this study extends the understanding of limb pattern formation and reveals novel findings concerning proximo-distal differences and migratory pathways. The discovery of Lmx1b expression in organs and its detailed description forms an important basis for further investigations to finally understand and treat human NPS.","Das Lmx1b-Gen kodiert für einen Transkriptionsfaktor mit LIM- und Homöodomänen. Die Ausschaltung dieses Gens bei Mäusen führt zu biventralen Extremitäten und Defekten in Skelett, Gehirn, in der Niere und in den Augen (Chen et al. 1998a). Ähnliche Defekte sind beim humanen Nail-Patella-Syndrom (NPS) beschrieben. Die genaue Untersuchung der Expression von Lmx1b in Mäusen wurde durch Einfügung eines LacZ Reportergens ermöglicht, das vom endogenen Lmx1b Promotor kontrolliert wird. Diese Arbeit gewährt einen neuen Einblick in das Expressionsmuster dieses Gens, wobei auch bisher unbeschriebene Organe untersucht und die dortige Expression detailliert charakterisiert werden. So wird zum ersten Mal gezeigt, dass Lmx1b in allen Stadien der Brustdrüsenentwicklung exprimiert ist. Nur die luminal gelegenen Epithelzellen erweisen sich als positiv. In Lmx1b Knock-out Mäusen fehlen die Brustdrüsen vollständig. Diese Erkenntnisse weisen darauf hin, dass Lmx1b eine wichtige Rolle in der Brustdrüsenentwicklung spielt. Tatsächlich wurde bei Patientinnen mit NPS eine Minderentwicklung der Brust beschrieben (Sweeney et al. 2003). Des Weiteren wird gezeigt, dass das Gen in der Niere nur in den Podozyten exprimiert ist. Dies könnte mit der Nephropathie von NPS Patienten in Zusammenhang stehen. In Leber, Herz und Milz hingegen wurde keine Expression von Lmx1b gefunden. Außerdem wird gezeigt, dass Lmx1b in allen Stadien der Extremitätenentwicklung im dorsalen Teil exprimiert ist. Die bis zur Mitte reichende Expression grenzt die dorsale Seite scharf nach ventral ab. Zellkulturversuche mit gemischten dorsalen und ventralen Zellen ergaben, dass beide Populationen homogen verteilt bleiben und sich nicht aussortieren. Dies weist darauf hin, dass die scharfe Grenze nicht durch unterschiedliche Zelladhäsion aller Extremitätenzellen zu erklären ist, sondern vielleicht nur im Bereich der Grenze selbst besteht. Transplantationsexperimente zwischen Wachtel- und Hühnerembryonen zeigen, dass wandernde Zellen die dorso-ventrale Grenze nicht überschreiten. In die Extremität einwandernde myogene Vorläuferzellen haben sich als Lmx1b negativ erwiesen und vermutlich wird Lmx1b auch in differenzierten Muskelzellen nicht exprimiert. In dieser Arbeit werden zudem neue Wanderungswege und unterschiedliches Verhalten entlang der Grundachsen von Muskelvorläuferzellen beschrieben. Die Entdeckung von Lmx1b in weiteren Organen und die detaillierte Beschreibung seiner Expression stellt eine wichtige Grundlage für die weitere Forschung dar. Sie trägt dazu bei, das menschliche NPS besser zu verstehen und möglicherweise eines Tages behandeln zu können."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Detailed analysis of Lmx1b expression in multiple organs and its role in dorso-ventral patterning with emphasis on myogenic precursor cells","Detaillierte Analyse der Lmx1b-Expression in verschiedenen Organen und seine Rolle in der dorso-ventralen Musterbildung unter besonderer Betrachtung von Muskelvorläuferzellen"]}]}],"canonical_facts":{"dc:contributor":["Brand-Saberi, Beate"],"dc:creator":["Schweizer, Heiko"],"dc:description.abstract":["Lmx1b belongs to a family of LIM homeodomain transcription factors expressed in multiple organs. Targeted disruption of Lmx1b results in ventralization of the limbs, skeletal, brain, kidney and ocular defects which resembles the corresponding human Nail-Patella Syndrome (NPS) (Chen et al. 1998a). The generation of transgenic mice carrying a LacZ reporter gene under the control of the endogenous Lmx1b locus allowed detailed analysis of Lmx1b expression. This study provides novel insights in the expression pattern, determines precisely Lmx1b-positive cell types in tissues, and describes for the first time expression in organs. It was demonstrated that Lmx1b expression is present throughout all stages of mammary gland development and restricted to luminal epithelial cells. Mice targeted for Lmx1b lack mammary glands. These findings indicate that Lmx1b plays a pivotal role in mammary gland development. Indeed, female patients with NPS display poor breast development (Sweeney et al. 2003). It is shown that Lmx1b expression is restricted to podocytes in the kidney, indicating the involvement of Lmx1b in nephropathy of NPS patients. No expression was detected in heart, liver and spleen. Lmx1b is involved in pattern formation of the limb and exhibits expression throughout all stages of embryonic development restricted to the dorsal limb mesenchyme. Hereby, Lmx1b expression marks a sharp boundary towards the ventral part of the limb. It is shown that dorsal Lmx1b-positive cells do not sort out from ventral Lmx1b-negative cells. This suggests that the maintenance of the boundary is not triggered by differential cell adhesion in the whole limb, maybe only at the boundary itself. <br>Moreover, interspecific grafting experiments using quail-chick chimeras showed that migrating cells have restricted movement within the dorsal or ventral compartment they attain during transplantation. These findings indicate that migrating cells respect the boundary between the dorsal and ventral compartment and no exchange occurs. Interestingly, although Lmx1b is known as a marker for the dorsal limb mesenchyme, myogenic precursor cells invading the dorsal part of the limb are shown to be devoid of expression. It is also assumed that differentiated muscle lacks Lmx1b expression. In all, this study extends the understanding of limb pattern formation and reveals novel findings concerning proximo-distal differences and migratory pathways. The discovery of Lmx1b expression in organs and its detailed description forms an important basis for further investigations to finally understand and treat human NPS.","Das Lmx1b-Gen kodiert für einen Transkriptionsfaktor mit LIM- und Homöodomänen. Die Ausschaltung dieses Gens bei Mäusen führt zu biventralen Extremitäten und Defekten in Skelett, Gehirn, in der Niere und in den Augen (Chen et al. 1998a). Ähnliche Defekte sind beim humanen Nail-Patella-Syndrom (NPS) beschrieben. Die genaue Untersuchung der Expression von Lmx1b in Mäusen wurde durch Einfügung eines LacZ Reportergens ermöglicht, das vom endogenen Lmx1b Promotor kontrolliert wird. Diese Arbeit gewährt einen neuen Einblick in das Expressionsmuster dieses Gens, wobei auch bisher unbeschriebene Organe untersucht und die dortige Expression detailliert charakterisiert werden. So wird zum ersten Mal gezeigt, dass Lmx1b in allen Stadien der Brustdrüsenentwicklung exprimiert ist. Nur die luminal gelegenen Epithelzellen erweisen sich als positiv. In Lmx1b Knock-out Mäusen fehlen die Brustdrüsen vollständig. Diese Erkenntnisse weisen darauf hin, dass Lmx1b eine wichtige Rolle in der Brustdrüsenentwicklung spielt. Tatsächlich wurde bei Patientinnen mit NPS eine Minderentwicklung der Brust beschrieben (Sweeney et al. 2003). Des Weiteren wird gezeigt, dass das Gen in der Niere nur in den Podozyten exprimiert ist. Dies könnte mit der Nephropathie von NPS Patienten in Zusammenhang stehen. In Leber, Herz und Milz hingegen wurde keine Expression von Lmx1b gefunden. Außerdem wird gezeigt, dass Lmx1b in allen Stadien der Extremitätenentwicklung im dorsalen Teil exprimiert ist. Die bis zur Mitte reichende Expression grenzt die dorsale Seite scharf nach ventral ab. Zellkulturversuche mit gemischten dorsalen und ventralen Zellen ergaben, dass beide Populationen homogen verteilt bleiben und sich nicht aussortieren. Dies weist darauf hin, dass die scharfe Grenze nicht durch unterschiedliche Zelladhäsion aller Extremitätenzellen zu erklären ist, sondern vielleicht nur im Bereich der Grenze selbst besteht. Transplantationsexperimente zwischen Wachtel- und Hühnerembryonen zeigen, dass wandernde Zellen die dorso-ventrale Grenze nicht überschreiten. In die Extremität einwandernde myogene Vorläuferzellen haben sich als Lmx1b negativ erwiesen und vermutlich wird Lmx1b auch in differenzierten Muskelzellen nicht exprimiert. In dieser Arbeit werden zudem neue Wanderungswege und unterschiedliches Verhalten entlang der Grundachsen von Muskelvorläuferzellen beschrieben. Die Entdeckung von Lmx1b in weiteren Organen und die detaillierte Beschreibung seiner Expression stellt eine wichtige Grundlage für die weitere Forschung dar. Sie trägt dazu bei, das menschliche NPS besser zu verstehen und möglicherweise eines Tages behandeln zu können."],"dc:format.medium":["application/pdf"],"dc:subject":["Extremitäten","Brustdrüsen","Reportergen","Lbx1","Muskelvorläuferzellen","Muskelentwicklung","Lmx1b","cell migration","Nail-Patella-Syndrome","mammary gland development"],"dc:title":["Detailed analysis of Lmx1b expression in multiple organs and its role in dorso-ventral patterning with emphasis on myogenic precursor cells","Detaillierte Analyse der Lmx1b-Expression in verschiedenen Organen und seine Rolle in der dorso-ventralen Musterbildung unter besonderer Betrachtung von Muskelvorläuferzellen"],"dc:type":["DoctoralThesis"]},"updated_at":"2026-07-24T02:22:28Z"}