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Hes1 is required for appropriate morphogenesis and differentiation during mouse thyroid gland development.

Carre A, Rachdi L, Tron E, Richard B, Castanet M, Schlumberger M, Bidart JM, Szinnai G, Polak M - PLoS ONE (2011)

Bottom Line: After fusion of thyroid anlages, hypoplastic Hes1(-/-) thyroids revealed a significantly decreased labelling area for T4 (-78%) and calcitonin (-65%) normalized to Nkx2-1 positive cells.Decreased T4-synthesis might be due to reduced Nis labelling area (-69%).These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells.

View Article: PubMed Central - PubMed

Affiliation: INSERM U845, UniversitΓ© Paris-Descartes, Paris, France.

ABSTRACT
Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1(-/-) mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1(-/-) mouse embryos showed a significantly smaller total thyroid surface area (-40 to -60%) compared to wild type mice at all study time points (E9.5-E16.5). In both Hes1(-/-) and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1(-/-) mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1(-/-) thyroids revealed a significantly decreased labelling area for T4 (-78%) and calcitonin (-65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (-69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells.

Show MeSH
Nis protein expression and quantification in Hes1βˆ’/βˆ’ thyroids.The Nkx2-1 staining in A and D localizes the thyroid gland. In B, C, E, F, Nis protein labelled thyrocytes. In C and F, co-staining of Nis and Hoechst visualizes Nis in the basolateral membrane of the thyrocytes and Hoechst in the nucleus of the thyrocytes. In G, Nis surface areas were quantified at E16.5 in wild type and Hes1βˆ’/βˆ’ mice and compared to the Nkx2-1-positive total thyroid surface area. Three embryos per genotype were used for quantification.Chi-square test, * p<0.05.
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pone-0016752-g005: Nis protein expression and quantification in Hes1βˆ’/βˆ’ thyroids.The Nkx2-1 staining in A and D localizes the thyroid gland. In B, C, E, F, Nis protein labelled thyrocytes. In C and F, co-staining of Nis and Hoechst visualizes Nis in the basolateral membrane of the thyrocytes and Hoechst in the nucleus of the thyrocytes. In G, Nis surface areas were quantified at E16.5 in wild type and Hes1βˆ’/βˆ’ mice and compared to the Nkx2-1-positive total thyroid surface area. Three embryos per genotype were used for quantification.Chi-square test, * p<0.05.

Mentions: Ferretti et al. have shown that Nis was an apparent Hes1 target gene. Indeed, HES1 transactivated NIS directly in human adult thyrocytes [13]. Nis promotes the active iodide uptake by the thyrocytes, which is a crucial step for the onset of thyroid hormone synthesis and is expressed from E15.5 onwards in mice [18]. Thus, we quantified the Nis-positive surface area in relation to the total Nkx2-1 positive surface area in Hes1βˆ’/βˆ’ vs. wild type mice. The ratio of Nis-positive to Nkx2-1 positive surface area at E16.5 was 69% lower in Hes1βˆ’/βˆ’ mice than in wild type mice (p<0.05) (Figure 5A–G) reflecting a reduced iodide uptake capacity.


Hes1 is required for appropriate morphogenesis and differentiation during mouse thyroid gland development.

Carre A, Rachdi L, Tron E, Richard B, Castanet M, Schlumberger M, Bidart JM, Szinnai G, Polak M - PLoS ONE (2011)

Nis protein expression and quantification in Hes1βˆ’/βˆ’ thyroids.The Nkx2-1 staining in A and D localizes the thyroid gland. In B, C, E, F, Nis protein labelled thyrocytes. In C and F, co-staining of Nis and Hoechst visualizes Nis in the basolateral membrane of the thyrocytes and Hoechst in the nucleus of the thyrocytes. In G, Nis surface areas were quantified at E16.5 in wild type and Hes1βˆ’/βˆ’ mice and compared to the Nkx2-1-positive total thyroid surface area. Three embryos per genotype were used for quantification.Chi-square test, * p<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045378&req=5

pone-0016752-g005: Nis protein expression and quantification in Hes1βˆ’/βˆ’ thyroids.The Nkx2-1 staining in A and D localizes the thyroid gland. In B, C, E, F, Nis protein labelled thyrocytes. In C and F, co-staining of Nis and Hoechst visualizes Nis in the basolateral membrane of the thyrocytes and Hoechst in the nucleus of the thyrocytes. In G, Nis surface areas were quantified at E16.5 in wild type and Hes1βˆ’/βˆ’ mice and compared to the Nkx2-1-positive total thyroid surface area. Three embryos per genotype were used for quantification.Chi-square test, * p<0.05.
Mentions: Ferretti et al. have shown that Nis was an apparent Hes1 target gene. Indeed, HES1 transactivated NIS directly in human adult thyrocytes [13]. Nis promotes the active iodide uptake by the thyrocytes, which is a crucial step for the onset of thyroid hormone synthesis and is expressed from E15.5 onwards in mice [18]. Thus, we quantified the Nis-positive surface area in relation to the total Nkx2-1 positive surface area in Hes1βˆ’/βˆ’ vs. wild type mice. The ratio of Nis-positive to Nkx2-1 positive surface area at E16.5 was 69% lower in Hes1βˆ’/βˆ’ mice than in wild type mice (p<0.05) (Figure 5A–G) reflecting a reduced iodide uptake capacity.

Bottom Line: After fusion of thyroid anlages, hypoplastic Hes1(-/-) thyroids revealed a significantly decreased labelling area for T4 (-78%) and calcitonin (-65%) normalized to Nkx2-1 positive cells.Decreased T4-synthesis might be due to reduced Nis labelling area (-69%).These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells.

View Article: PubMed Central - PubMed

Affiliation: INSERM U845, UniversitΓ© Paris-Descartes, Paris, France.

ABSTRACT
Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1(-/-) mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1(-/-) mouse embryos showed a significantly smaller total thyroid surface area (-40 to -60%) compared to wild type mice at all study time points (E9.5-E16.5). In both Hes1(-/-) and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1(-/-) mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1(-/-) thyroids revealed a significantly decreased labelling area for T4 (-78%) and calcitonin (-65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (-69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells.

Show MeSH