Molecular Mechanisms of Thyroid Dysgenesis

Polak, Michel; Sura-Trueba, Sylvia; Chauty, Anne; Szinnai, Gabor; Carré, Aurore; Castanet, Mireille

doi:10.1159/000080494

Cited by 31 publications

(27 citation statements)

References 87 publications

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“…MO-mediated gene knock-down has successfully been used to delineate the role of various genes during zebrafish thyroid organogenesis including nkx2.1a [22], hhex [22], tshr [26], vegfa [14], jag1a [75], jag1b [75], bcl2l [76] and ltbp3 [15]. Notably, MO-mediated knock-down of nkx2.1a [22] and tshr [26] function in zebrafish embryos recapitulated thyroid phenotypes observed in CH patients and mouse models with inactivating mutations of NKX2.1 (hypoplasia, athyreosis) and TSHR (hypofunctional gland with reduced number of follicles) [1,2,3,4,5,6]. These data clearly strengthen the view of zebrafish as a valuable system to model congenital thyroid diseases.…”

Section: Perspectives For Modeling Human Thyroid Diseases In Zebrafishmentioning

confidence: 99%

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New Model Systems to Illuminate Thyroid Organogenesis. Part I: An Update on the Zebrafish Toolbox

2013

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Thyroid dysgenesis (TD) resulting from defects during embryonic thyroid development represents a major cause of congenital hypothyroidism. The pathogenetic mechanisms of TD in human newborns, however, are still poorly understood and disease-causing genetic variants have been identified in only a small percentage of TD cases. This limited understanding of the pathogenesis of TD is partly due to a lack of knowledge on how intrinsic factors and extrinsic signalling cues orchestrate the differentiation of thyroid follicular cells and the morphogenesis of thyroid tissue. Recently, embryonic stem cells and zebrafish embryos emerged as novel model systems that allow for innovative experimental approaches in order to decipher cellular and molecular mechanisms of thyroid development and to unravel pathogenic mechanisms of TD. Zebrafish embryos offer several salient properties for studies on thyroid organogenesis including rapid and external development, optical transparency, ease of breeding, relative short generation time and amenability for genome editing. In this review, we will highlight recent advances in the zebrafish toolkit to visualize cellular dynamics of organ development and discuss specific prospects of the zebrafish model for studies on vertebrate thyroid development and human congenital thyroid diseases.

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Section: Perspectives For Modeling Human Thyroid Diseases In Zebrafishmentioning

confidence: 99%

“…All these phenotypes are considered to result from defects in embryonic thyroid development. The molecular mechanisms underlying TD in human newborns, however, remain poorly understood to date [2,5]. This is, in part, due to our still limited understanding on how the function of intrinsic factors (e.g.…”

Section: Introductionmentioning

confidence: 99%

New Model Systems to Illuminate Thyroid Organogenesis. Part I: An Update on the Zebrafish Toolbox

2013

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“…The thyroid gland develops from a midline thickening of the pharyngeal floor and paired caudal extensions of the fourth pharyngobranchial pouches [5, 6]. In the human fetus, at 7 weeks of development, these structures have fused and the thyroid gland has migrated to its definitive position in the anterior neck.…”

Section: Normal Thyroid Gland Functionmentioning

confidence: 99%

Congenital Hyperthyroidism: The Fetus as a Patient

et al. 2006

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Congenital hyperthyroidism is less frequent than congenital hypothyroidism but its impact on growth and development can be as dramatic. The immune form of hyperthyroidism that is transmitted from a mother with Graves’ disease to her foetus and then neonate is transient, but cases of persistent congenital hyperthyroidism had also been described, that can now be explained by molecular abnormalities of the thyrotropin receptor. The abundance of published data on the neonatal effects of maternal Graves’ disease contrasts with the paucity of information on fetal effects. Recent studies showed that it is of utmost to scrutinize fetal thyroid by expert ultrasonographist and to have a team work with obstetricians and pediatric endocrinologists in pregnant women with Graves’ disease. This allowed to accurately determine the fetal thyroid status and to adapt the treatment in the mothers successfully. Fetal hyperthyroidism does exist and needs an appropriate aggressive treatment. Clearly the fetus has become our patient!

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“…TTF1, FOXE1 and PAX8 in thyroid embryogenesis, mutations in their genes have been proposed as a genetic background of TD [1]. However, to date, changes in these factors account only for less than 5%, mostly syndromic cases, while the etiology of the vast majority of isolated TD remains to be discovered [2]. …”

Section: Introductionmentioning

confidence: 99%

FOXE1 Polyalanine Tract Length Polymorphism in Patients with Thyroid Hemiagenesis and Subjects with Normal Thyroid

Szczepanek¹,

Ruchała²,

Szaflarski³

et al. 2011

Horm Res Paediatr

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Background/Aims: Recent studies have pointed to the correlation between FOXE1 polyalanine tract (FOXE1-polyAla) length polymorphism and genetic susceptibility to thyroid dysgenesis causing congenital hypothyroidism. The objective of this study was a first assessment of the role of FOXE1-polyAla expansion in the genetic background of thyroid hemiagenesis (TH). Methods: The group studied consisted of 40 patients with TH, including 6 familial cases and a control group of 89 subjects with a normal thyroid. The polyAla tract and flanking sequence of FOXE1 was amplified using conventional PCR. Subsequently, capillary electrophoresis was performed to estimate the length of products. Results: A short variant of FOXE1-polyAla, containing 12 alanines, was present in 5 control subjects (5.6%), but was not found in TH. The incidence of longer variants (≧16 codons) of FOXE1-polyAla was significantly higher in patients with the familial form of TH in comparison to those with sporadic TH (p = 0.003) and controls (p = 0.005). Conclusions: There is high polymorphic variability of FOXE1-polyAla in both groups. Shorter variants of FOXE1-polyAla are underrepresented in subjects with familial TH. Therefore, FOXE1-polyAla tract expansion may contribute to the molecular background of familial but not sporadic forms of TH. Further studies are still required to confirm such findings.

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Molecular Mechanisms of Thyroid Dysgenesis

Cited by 31 publications

References 87 publications

New Model Systems to Illuminate Thyroid Organogenesis. Part I: An Update on the Zebrafish Toolbox

New Model Systems to Illuminate Thyroid Organogenesis. Part I: An Update on the Zebrafish Toolbox

Congenital Hyperthyroidism: The Fetus as a Patient

FOXE1 Polyalanine Tract Length Polymorphism in Patients with Thyroid Hemiagenesis and Subjects with Normal Thyroid

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