The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
Nancy R Manley - One of the best experts on this subject based on the ideXlab platform.
-
Tissue-specific roles for sonic hedgehog signaling in establishing thymus and Parathyroid organ fate
Development (Cambridge England), 2016Co-Authors: Virginia E. Bain, Julie Gordon, John D. O'neil, Isaias Ramos, Ellen R. Richie, Nancy R ManleyAbstract:The thymus and Parathyroids develop from third pharyngeal pouch (3rd pp) endoderm. Our previous studies show that Shh null mice have smaller, aParathyroid primordia in which thymus fate specification extends into the pharynx. SHH signaling is active in both dorsal pouch endoderm and neighboring neural crest (NC) mesenchyme. It is unclear which target tissue of SHH signaling is required for the patterning defects in Shh mutants. Here, we used a genetic approach to ectopically activate or delete the SHH signal transducer Smo in either pp endoderm or NC mesenchyme. Although no manipulation recapitulated the Shh null phenotype, manipulation of SHH signaling in either the endoderm or NC mesenchyme had direct and indirect effects on both cell types during fate specification and organogenesis. SHH pathway activation throughout pouch endoderm activated ectopic Tbx1 expression and partially suppressed the thymus-specific transcription factor Foxn1, identifying Tbx1 as a key target of SHH signaling in the 3rd pp. However, ectopic SHH signaling was insufficient to expand the GCM2-positive Parathyroid domain, indicating that multiple inputs, some of which might be independent of SHH signaling, are required for Parathyroid fate specification. These data support a model in which SHH signaling plays both positive and negative roles in patterning and organogenesis of the thymus and Parathyroids.
-
Thymus-Associated Parathyroid Hormone Has Two Cellular Origins with Distinct Endocrine and Immunological Functions
2013Co-Authors: Zhijie Liu, Alison Farley, Beth J. Kirby, Clare C Blackburn, Lizhen Chen, Christopher S Kovacs, Nancy R ManleyAbstract:In mammals, Parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the Parathyroid glands were thought to be the only source of PTH, extra-Parathyroid PTH production in the thymus, which shares a common origin with Parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aParathyroid Gcm2 2/2 mutants. However, the developmental ontogeny and cellular identity of these ‘‘thymic’ ’ PTH–expressing cells is unknown. We found that the lethality of aParathyroid Gcm2 2/2 mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-Parathyroid PTH in wild-type mice. Incomplete separation of the Parathyroid and thymus organs during organogenesis resulted in misplaced, isolated Parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and Parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human Parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2 2/2 mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does no
-
thymus associated Parathyroid hormone has two cellular origins with distinct endocrine and immunological functions
PLOS Genetics, 2010Co-Authors: Alison Farley, Beth J. Kirby, Clare C Blackburn, Lizhen Chen, Christopher S Kovacs, Nancy R ManleyAbstract:In mammals, Parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the Parathyroid glands were thought to be the only source of PTH, extra-Parathyroid PTH production in the thymus, which shares a common origin with Parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aParathyroid Gcm2−/− mutants. However, the developmental ontogeny and cellular identity of these “thymic” PTH–expressing cells is unknown. We found that the lethality of aParathyroid Gcm2−/− mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-Parathyroid PTH in wild-type mice. Incomplete separation of the Parathyroid and thymus organs during organogenesis resulted in misplaced, isolated Parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and Parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human Parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2−/− mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or Parathyroid function. We further show that the normal process of Parathyroid organogenesis in both mice and humans leads to the generation of multiple small Parathyroid clusters in addition to the main Parathyroid glands, that are the likely source of physiologically relevant “thymic PTH.”
-
gcm2 is required for the differentiation and survival of Parathyroid precursor cells in the Parathyroid thymus primordia
Developmental Biology, 2007Co-Authors: Zhijie Liu, Nancy R ManleyAbstract:Abstract The Parathyroid glands develop with the thymus from bilateral common primordia that develop from the 3rd pharyngeal pouch endoderm in mouse embryos at about E11, each of which separates into one Parathyroid gland and one thymus lobe by E13.5. Gcm2, a mouse ortholog of the Drosophila Glial Cells Missing gene, is expressed in the Parathyroid-specific domains in the 3rd pouches from E9.5. The null mutation of Gcm2 causes aParathyroidism in the fetal and adult mouse and has been proposed to be a master regulator for Parathyroid development. In order to study how Gcm2 functions in Parathyroid development, we investigated the mechanism that causes the loss of Parathyroids in Gcm2 null mutants. Analysis of the 3rd pouch-derived primordium in Gcm2−/− mutants showed the Parathyroid-specific domain was present before E12.5 but underwent programmed cell death between E12 and 12.5. RNA and protein localization studies for Parathyroid hormone (Pth) in wild-type embryos showed that the presumptive Parathyroid domain in the Parathyroid/thymus primordia started to transcribe Pth mRNA and produce PTH protein from E11.5 before the separation of Parathyroid and thymus domains. However in Gcm2−/− mutants, the Parathyroid-specific domain in the common primordium did not express Pth and could not maintain the expression of two other Parathyroid marker genes, CasR and CCL21, although expression of these two genes was initiated. Marker gene analysis placed Gcm2 downstream of the known transcription and signaling pathways for Parathyroid/thymus organogenesis. These results suggest that Gcm2 is not required for pouch patterning or to establish the Parathyroid domain, but is required for differentiation and subsequent survival of Parathyroid cells.
-
Gcm2 is required for the differentiation and survival of Parathyroid precursor cells in the Parathyroid/thymus primordia
Developmental biology, 2007Co-Authors: Zhijie Liu, Nancy R ManleyAbstract:Abstract The Parathyroid glands develop with the thymus from bilateral common primordia that develop from the 3rd pharyngeal pouch endoderm in mouse embryos at about E11, each of which separates into one Parathyroid gland and one thymus lobe by E13.5. Gcm2, a mouse ortholog of the Drosophila Glial Cells Missing gene, is expressed in the Parathyroid-specific domains in the 3rd pouches from E9.5. The null mutation of Gcm2 causes aParathyroidism in the fetal and adult mouse and has been proposed to be a master regulator for Parathyroid development. In order to study how Gcm2 functions in Parathyroid development, we investigated the mechanism that causes the loss of Parathyroids in Gcm2 null mutants. Analysis of the 3rd pouch-derived primordium in Gcm2−/− mutants showed the Parathyroid-specific domain was present before E12.5 but underwent programmed cell death between E12 and 12.5. RNA and protein localization studies for Parathyroid hormone (Pth) in wild-type embryos showed that the presumptive Parathyroid domain in the Parathyroid/thymus primordia started to transcribe Pth mRNA and produce PTH protein from E11.5 before the separation of Parathyroid and thymus domains. However in Gcm2−/− mutants, the Parathyroid-specific domain in the common primordium did not express Pth and could not maintain the expression of two other Parathyroid marker genes, CasR and CCL21, although expression of these two genes was initiated. Marker gene analysis placed Gcm2 downstream of the known transcription and signaling pathways for Parathyroid/thymus organogenesis. These results suggest that Gcm2 is not required for pouch patterning or to establish the Parathyroid domain, but is required for differentiation and subsequent survival of Parathyroid cells.
S Wideehn - One of the best experts on this subject based on the ideXlab platform.
-
primary Parathyroid hyperplasia of water clear cell type transformation of water clear cells into chief cells
Apmis, 2009Co-Authors: S Persson, Goran K Hansson, I Hedman, L E Tisell, S WideehnAbstract:: An exceptional case of water-clear cell hyperplasia (WCCH) of the Parathyroid glands is presented. Parathyroid tissue was excised at three operations during a period of twenty years before the patient eventually became normocalcemic. Microscopic evaluation of the Parathyroids from the first operation showed typical WCCH-findings. However, the Parathyroid tissue excised at the last operation was composed of chief cells. There were calcifications and even bone formation. A pigment with the staining and electron-microscopic characteristics of lipofuscin was found in abundance. There were also a few oxyphils. This case shows that clear cells, originally derived from chief cells, can transform into chief cells again.
S Persson - One of the best experts on this subject based on the ideXlab platform.
-
primary Parathyroid hyperplasia of water clear cell type transformation of water clear cells into chief cells
Apmis, 2009Co-Authors: S Persson, Goran K Hansson, I Hedman, L E Tisell, S WideehnAbstract:: An exceptional case of water-clear cell hyperplasia (WCCH) of the Parathyroid glands is presented. Parathyroid tissue was excised at three operations during a period of twenty years before the patient eventually became normocalcemic. Microscopic evaluation of the Parathyroids from the first operation showed typical WCCH-findings. However, the Parathyroid tissue excised at the last operation was composed of chief cells. There were calcifications and even bone formation. A pigment with the staining and electron-microscopic characteristics of lipofuscin was found in abundance. There were also a few oxyphils. This case shows that clear cells, originally derived from chief cells, can transform into chief cells again.
Zhijie Liu - One of the best experts on this subject based on the ideXlab platform.
-
Thymus-Associated Parathyroid Hormone Has Two Cellular Origins with Distinct Endocrine and Immunological Functions
2013Co-Authors: Zhijie Liu, Alison Farley, Beth J. Kirby, Clare C Blackburn, Lizhen Chen, Christopher S Kovacs, Nancy R ManleyAbstract:In mammals, Parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the Parathyroid glands were thought to be the only source of PTH, extra-Parathyroid PTH production in the thymus, which shares a common origin with Parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aParathyroid Gcm2 2/2 mutants. However, the developmental ontogeny and cellular identity of these ‘‘thymic’ ’ PTH–expressing cells is unknown. We found that the lethality of aParathyroid Gcm2 2/2 mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-Parathyroid PTH in wild-type mice. Incomplete separation of the Parathyroid and thymus organs during organogenesis resulted in misplaced, isolated Parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and Parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human Parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2 2/2 mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does no
-
gcm2 is required for the differentiation and survival of Parathyroid precursor cells in the Parathyroid thymus primordia
Developmental Biology, 2007Co-Authors: Zhijie Liu, Nancy R ManleyAbstract:Abstract The Parathyroid glands develop with the thymus from bilateral common primordia that develop from the 3rd pharyngeal pouch endoderm in mouse embryos at about E11, each of which separates into one Parathyroid gland and one thymus lobe by E13.5. Gcm2, a mouse ortholog of the Drosophila Glial Cells Missing gene, is expressed in the Parathyroid-specific domains in the 3rd pouches from E9.5. The null mutation of Gcm2 causes aParathyroidism in the fetal and adult mouse and has been proposed to be a master regulator for Parathyroid development. In order to study how Gcm2 functions in Parathyroid development, we investigated the mechanism that causes the loss of Parathyroids in Gcm2 null mutants. Analysis of the 3rd pouch-derived primordium in Gcm2−/− mutants showed the Parathyroid-specific domain was present before E12.5 but underwent programmed cell death between E12 and 12.5. RNA and protein localization studies for Parathyroid hormone (Pth) in wild-type embryos showed that the presumptive Parathyroid domain in the Parathyroid/thymus primordia started to transcribe Pth mRNA and produce PTH protein from E11.5 before the separation of Parathyroid and thymus domains. However in Gcm2−/− mutants, the Parathyroid-specific domain in the common primordium did not express Pth and could not maintain the expression of two other Parathyroid marker genes, CasR and CCL21, although expression of these two genes was initiated. Marker gene analysis placed Gcm2 downstream of the known transcription and signaling pathways for Parathyroid/thymus organogenesis. These results suggest that Gcm2 is not required for pouch patterning or to establish the Parathyroid domain, but is required for differentiation and subsequent survival of Parathyroid cells.
-
Gcm2 is required for the differentiation and survival of Parathyroid precursor cells in the Parathyroid/thymus primordia
Developmental biology, 2007Co-Authors: Zhijie Liu, Nancy R ManleyAbstract:Abstract The Parathyroid glands develop with the thymus from bilateral common primordia that develop from the 3rd pharyngeal pouch endoderm in mouse embryos at about E11, each of which separates into one Parathyroid gland and one thymus lobe by E13.5. Gcm2, a mouse ortholog of the Drosophila Glial Cells Missing gene, is expressed in the Parathyroid-specific domains in the 3rd pouches from E9.5. The null mutation of Gcm2 causes aParathyroidism in the fetal and adult mouse and has been proposed to be a master regulator for Parathyroid development. In order to study how Gcm2 functions in Parathyroid development, we investigated the mechanism that causes the loss of Parathyroids in Gcm2 null mutants. Analysis of the 3rd pouch-derived primordium in Gcm2−/− mutants showed the Parathyroid-specific domain was present before E12.5 but underwent programmed cell death between E12 and 12.5. RNA and protein localization studies for Parathyroid hormone (Pth) in wild-type embryos showed that the presumptive Parathyroid domain in the Parathyroid/thymus primordia started to transcribe Pth mRNA and produce PTH protein from E11.5 before the separation of Parathyroid and thymus domains. However in Gcm2−/− mutants, the Parathyroid-specific domain in the common primordium did not express Pth and could not maintain the expression of two other Parathyroid marker genes, CasR and CCL21, although expression of these two genes was initiated. Marker gene analysis placed Gcm2 downstream of the known transcription and signaling pathways for Parathyroid/thymus organogenesis. These results suggest that Gcm2 is not required for pouch patterning or to establish the Parathyroid domain, but is required for differentiation and subsequent survival of Parathyroid cells.
Gunnar Westin - One of the best experts on this subject based on the ideXlab platform.
-
Parathyroid glands in calcium regulation and human disease.
Annals of the New York Academy of Sciences, 2005Co-Authors: Göran Åkerström, Per Hellman, Ola Hessman, Ulrika Segersten, Gunnar WestinAbstract:: In humans and other land-living vertebrates, the Parathyroids are known to have an overall regulatory role with action as a thermostat in the systemic calcium homeostasis to ensure tight regulation of serum calcium concentrations and appropriate skeletal mineralization. Parathyroid hormone (PTH) is an 84-amino-acid peptide, synthesized and released by Parathyroid chief cells in response to hypocalcemia. PTH mobilizes calcium by increasing calcium resorption from bone and by raising calcium reabsorption in the proximal kidney tubule. Treatment with active vitamin D can increase vitamin D receptor expression, inhibit growth of Parathyroid tumors, and reduce PTH levels in patients with hyperParathyroidism (HPT). Newly developed vitamin D analogues with reduced calcemic effects and with more pronounced antiproliferative effect may provide new favorable treatment for reversal of HPT.
