The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion that Tbx1 is required for thymus organogenesis, we have shown that ectopic expression of Tbx1 in thymic epithelial cells (TECs) suppresses FOXN1, inhibits TEC proliferation and arrests TEC differentiation, suggesting Tbx1 must be tightly regulated in the 3rd pp endoderm for proper thymus organogenesis to occur. Members of the miR-17-92 cluster downregulate Tbx1 in cardiac progenitor cells to permit cardiomyocyte differentiation, and we demonstrated that members of this cluster are expressed in the 3rd pp endoderm and mesenchyme. We find that global or TEC-specific deletion of miR-17-92 enhances TBX1 expression and reduces FOXN1 in the 3rd pp. Furthermore, global deletion of miR-17-92 results in an ectopic, hypoplastic thymus lobe, while deletion in TECs results in TBX1+ progenitor cells that persist in the fetal thymus. In contrast, overexpression of miR-17-92 in TECs results in downregulation of TBX1 in the dorsal 3rd pp and surrounding mesenchyme. Therefore, these data suggest that miR-17-92 plays an essential role in thymus development by regulating Tbx1 expression in the 3rd pp.
Additionally, previous work from our lab has shown that a genetic deficiency in neural crest cells (NCCs) expands thymus fate in the 3rd pp. We show that NCCs mediate this effect in part by promoting TBX1 expression in the dorsal 3rd pp. Finally, we present evidence consistent with the dual hypothesis that Fgf8 expression in the ventral 3rd pp promotes thymus fate by restricting TBX1. Based on these results, we generated a working model describing the signaling networks that contribute to thymus fate and 3rd pp patterning.
","abstract_html":"<p>The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3<sup>rd</sup> pps). By E11.5 during mouse development, cells committed to the thymus lineage express <em>Foxn1 </em>whereas PT-fated cells express <em>Gcm2</em>. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. <em>Tbx1</em> is initially expressed throughout the 3<sup>rd</sup> pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion that <em>Tbx1 </em>is required for thymus organogenesis, we have shown that ectopic expression of <em>Tbx1 </em>in thymic epithelial cells (TECs) suppresses FOXN1, inhibits TEC proliferation and arrests TEC differentiation, suggesting <em>Tbx1</em> must be tightly regulated in the 3<sup>rd</sup> pp endoderm for proper thymus organogenesis to occur. Members of the <em>miR-17-92 </em>cluster downregulate <em>Tbx1 </em>in cardiac progenitor cells to permit cardiomyocyte differentiation, and we demonstrated that members of this cluster are expressed in the 3<sup>rd</sup> pp endoderm and mesenchyme. We find that global or TEC-specific deletion of <em>miR-17-92 </em>enhances TBX1 expression and reduces FOXN1 in the 3<sup>rd</sup> pp. Furthermore, global deletion of <em>miR-17-92 </em>results in an ectopic, hypoplastic thymus lobe, while deletion in TECs results in TBX1<sup>+</sup> progenitor cells that persist in the fetal thymus. In contrast, overexpression of <em>miR-17-92 </em>in TECs results in downregulation of TBX1 in the dorsal 3<sup>rd</sup> pp and surrounding mesenchyme. Therefore, these data suggest that <em>miR-17-92</em> plays an essential role in thymus development by regulating <em>Tbx1</em> expression in the 3<sup>rd</sup> pp.</p> <p>Additionally, previous work from our lab has shown that a genetic deficiency in neural crest cells (NCCs) expands thymus fate in the 3<sup>rd</sup> pp. We show that NCCs mediate this effect in part by promoting TBX1 expression in the dorsal 3<sup>rd</sup> pp. Finally, we present evidence consistent with the dual hypothesis that <em>Fgf8</em> expression in the ventral 3<sup>rd</sup> pp promotes thymus fate by restricting TBX1. Based on these results, we generated a working model describing the signaling networks that contribute to thymus fate and 3<sup>rd</sup> pp patterning.</p>","abstract_has_math":false,"creators":["Reeh, Kaitlin A"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Ellen R. Richie, PhD","Sharon Y. R. Dent, PhD","Richard D. Wood"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-12-01T08:00:00Z","date_published":"2015-12-01T08:00:00Z","updated_at":"2026-07-24T05:50:24Z","subjects":["Thymus","Tbx1","Foxn1","miR-17-92","Developmental Biology","Medicine and Health Sciences","Other Immunology and Infectious Disease"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/635","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Ellen R. Richie, PhD","Sharon Y. R. Dent, PhD","Richard D. Wood"]},{"key":"dc:creator","label":"Author","values":["Reeh, Kaitlin A"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-12-02T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Thymus","Tbx1","Foxn1","miR-17-92","Developmental Biology","Medicine and Health Sciences","Other Immunology and Infectious Disease"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/635"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion that Tbx1 is required for thymus organogenesis, we have shown that ectopic expression of Tbx1 in thymic epithelial cells (TECs) suppresses FOXN1, inhibits TEC proliferation and arrests TEC differentiation, suggesting Tbx1 must be tightly regulated in the 3rd pp endoderm for proper thymus organogenesis to occur. Members of the miR-17-92 cluster downregulate Tbx1 in cardiac progenitor cells to permit cardiomyocyte differentiation, and we demonstrated that members of this cluster are expressed in the 3rd pp endoderm and mesenchyme. We find that global or TEC-specific deletion of miR-17-92 enhances TBX1 expression and reduces FOXN1 in the 3rd pp. Furthermore, global deletion of miR-17-92 results in an ectopic, hypoplastic thymus lobe, while deletion in TECs results in TBX1+ progenitor cells that persist in the fetal thymus. In contrast, overexpression of miR-17-92 in TECs results in downregulation of TBX1 in the dorsal 3rd pp and surrounding mesenchyme. Therefore, these data suggest that miR-17-92 plays an essential role in thymus development by regulating Tbx1 expression in the 3rd pp.
Additionally, previous work from our lab has shown that a genetic deficiency in neural crest cells (NCCs) expands thymus fate in the 3rd pp. We show that NCCs mediate this effect in part by promoting TBX1 expression in the dorsal 3rd pp. Finally, we present evidence consistent with the dual hypothesis that Fgf8 expression in the ventral 3rd pp promotes thymus fate by restricting TBX1. Based on these results, we generated a working model describing the signaling networks that contribute to thymus fate and 3rd pp patterning.
"]},{"key":"dc:title","label":"Title","values":["Defining The Molecular Networks Necessary For Thymus Fate and Organogenesis"]}]}],"canonical_facts":{"dc:contributor":["Ellen R. Richie, PhD","Sharon Y. R. Dent, PhD","Richard D. Wood"],"dc:creator":["Reeh, Kaitlin A"],"dc:date.available":["2016-12-02T08:00:00Z"],"dc:description.abstract":["The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion that Tbx1 is required for thymus organogenesis, we have shown that ectopic expression of Tbx1 in thymic epithelial cells (TECs) suppresses FOXN1, inhibits TEC proliferation and arrests TEC differentiation, suggesting Tbx1 must be tightly regulated in the 3rd pp endoderm for proper thymus organogenesis to occur. Members of the miR-17-92 cluster downregulate Tbx1 in cardiac progenitor cells to permit cardiomyocyte differentiation, and we demonstrated that members of this cluster are expressed in the 3rd pp endoderm and mesenchyme. We find that global or TEC-specific deletion of miR-17-92 enhances TBX1 expression and reduces FOXN1 in the 3rd pp. Furthermore, global deletion of miR-17-92 results in an ectopic, hypoplastic thymus lobe, while deletion in TECs results in TBX1+ progenitor cells that persist in the fetal thymus. In contrast, overexpression of miR-17-92 in TECs results in downregulation of TBX1 in the dorsal 3rd pp and surrounding mesenchyme. Therefore, these data suggest that miR-17-92 plays an essential role in thymus development by regulating Tbx1 expression in the 3rd pp.
Additionally, previous work from our lab has shown that a genetic deficiency in neural crest cells (NCCs) expands thymus fate in the 3rd pp. We show that NCCs mediate this effect in part by promoting TBX1 expression in the dorsal 3rd pp. Finally, we present evidence consistent with the dual hypothesis that Fgf8 expression in the ventral 3rd pp promotes thymus fate by restricting TBX1. Based on these results, we generated a working model describing the signaling networks that contribute to thymus fate and 3rd pp patterning.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/635"],"dc:subject":["Thymus","Tbx1","Foxn1","miR-17-92","Developmental Biology","Medicine and Health Sciences","Other Immunology and Infectious Disease"],"dc:title":["Defining The Molecular Networks Necessary For Thymus Fate and Organogenesis"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:24Z"}