Gcm2 is required for the differentiation and survival of parathyroid precursor cells in the parathyroid/thymus primordia

Liu, Zhijie; Yu, Shannon F.; Manley, Nancy R.

doi:10.1016/j.ydbio.2007.02.014

Cited by 121 publications

(140 citation statements)

References 73 publications

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“…Deficiency of Gcm2 in mice leads to the absence of parathyroid glands without affecting thymus formation (Liu et al, 2007). Notch-target Gata3 (Fang et al, 2007;Naito et al, 2011) is one of the upstream regulators of Gcm2, as Gata3 -/-mice showed no Gcm2 expression and no gland formation (Grigorieva et al, 2010).…”

Section: Parathyroid Rudimentmentioning

confidence: 99%

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Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

Figueiredo

Silva

Santos

et al. 2016

Developmental Biology

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Neves, Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ f o r m a t i o n , Developmental Biology, http://dx.doi.org/10. 1016/j.ydbio.2016.08.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe avian thymus and parathyroids (T/PT) common primordium derives from the endoderm of the third and fourth pharyngeal pouches (3/4PP). The molecular mechanisms that govern T/PT development are not fully understood. Here we study the effects of Notch and Hedgehog (Hh) signalling modulation during common primordium development using in vitro, in vivo and in ovo approaches. The impairment of Notch activity reduced Foxn1/thymus-fated and Gcm2/Pth/parathyroid-fated domains in the 3/4PP and further compromised the development of the parathyroid glands. When Hh signalling was abolished, we observed a reduction in the Gata3/Gcm2-and Lfng-expression domains at the median/anterior and median/posterior territories of the pouches, respectively. In contrast, the Foxn1 expression- This study offers novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner.

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Section: Parathyroid Rudimentmentioning

confidence: 99%

“…homozygous null mutant mice, the expression of Pth is not initiated and no parathyroid glands are formed (Günther et al, 2000;Liu et al, 2007).…”

mentioning

confidence: 99%

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

Figueiredo

Silva

Santos

et al. 2016

Developmental Biology

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“…By E11.5, the thymus-and parathyroid-fated domains can be recognized by Foxn1 and Gcm2 expression respectively. However, although these transcription factors regulate differentiation, they do not specify thymus versus parathyroid fate (Bleul et al, 2006;Liu et al, 2007;Nowell et al, 2011). A Hox-Pax-Eya-Six cascade is implicated upstream of thymus specification, but has not been directly linked to the establishment of thymus fate (Manley and Condie, 2010).…”

Section: Introductionmentioning

confidence: 99%

Ectopic TBX1 suppresses thymic epithelial cell differentiation and proliferation during thymus organogenesis

et al. 2014

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The thymus and parathyroid glands arise from a shared endodermal primordium in the third pharyngeal pouch (3rd pp). Thymus fate is specified in the ventral 3rd pp between E9.5 and E11, whereas parathyroid fate is specified in the dorsal domain. The molecular mechanisms that specify fate and regulate thymus and parathyroid development are not fully delineated. Previous reports suggested that Tbx1 is required for thymus organogenesis because loss of Tbx1 in individuals with DiGeorge syndrome and in experimental Tbx1 deletion mutants is associated with thymus aplasia or hypoplasia. However, the thymus phenotype is likely to be secondary to defects in pharyngeal pouch formation. Furthermore, the absence of Tbx1 expression in the thymus-fated domain of the wild-type 3rd pp suggested that Tbx1 is instead a negative regulator of thymus organogenesis. To test this hypothesis, we generated a novel mouse strain in which expression of a conditional Tbx1 allele was ectopically activated in the thymus-fated domain of the 3rd pp. Ectopic Tbx1 expression severely repressed expression of Foxn1, a transcription factor that marks the thymus-fated domain and is required for differentiation and proliferation of thymic epithelial cell (TEC) progenitors. By contrast, ectopic Tbx1 did not alter the expression pattern of Gcm2, a transcription factor restricted to the parathyroidfated domain and required for parathyroid development. Ectopic Tbx1 expression impaired TEC proliferation and arrested TEC differentiation at an early progenitor stage. The results support the hypothesis that Tbx1 negatively regulates TEC growth and differentiation, and that extinction of Tbx1 expression in 3rd pp endoderm is a prerequisite for thymus organogenesis.

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“…The first-identified drosophila GCM was identified as a gene responsible for a phenotype called glial cells missing, which is the gene name GCM derived (19,23). GCMa and GCMb are predominantly expressed in developing placenta and the parathyroid gland, respectively (5,16,29). GCMa instructs trophoblast stem cells to differentiate into syncytiotrophoblast cells (1,2).…”

Section: Introductionmentioning

confidence: 99%

PMA-induced GCMa phosphorylation stimulates its transcriptional activity and degradation

et al. 2012

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Glial cells missing Drosophila homolog a (GCMa) is a member of the GCM transcription factor family and plays critical roles in trophoblast differentiation and placental functions. It is well established that the cyclic AMP (cAMP)-dependent pathway induces the expression and transcriptional activity of GCMa by regulating post-translational modifications of GCMa, which results in enhancement of trophoblast differentiation. We previously observed that phorbol 12-myristate 13-acetate (PMA) stimulates phosphorylation of GCMa on serines 328, 378 and 383 through the protein kinase C (PKC)-and mitogen-activated protein kinase kinase (MEK)/extracellular signalregulated kinase (ERK)-dependent pathway, which decreases the protein stability of GCMa. Here we report that PMA increases the ubiquitination level of GCMa, dependent on the phosphorylation of GCMa on serines 328, 378 and 383. We found that this phosphorylation also stimulates the transcriptional activity of GCMa. Our data indicate that the PMA-induced PKC-and MEK/ERKdependent pathway enhances the degradation as well as the transcriptional activity of GCMa. We also examined the impact of this signaling pathway on trophoblasts and the results suggest that the PKC-and MEK/ERK-dependent pathway is involved in the regulation of trophoblast differentiation.

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Gcm2 is required for the differentiation and survival of parathyroid precursor cells in the parathyroid/thymus primordia

Cited by 121 publications

References 73 publications

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

Ectopic TBX1 suppresses thymic epithelial cell differentiation and proliferation during thymus organogenesis

PMA-induced GCMa phosphorylation stimulates its transcriptional activity and degradation

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