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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, Université 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
Proposed roles of Hes1 during murine thyroid development and function.Hes1 controls the number of thyrocyte progenitors in the median anlage (in grey) at E9.5 and C-cell progenitors in the ultimobranchial bodies (in white) at E11.5. Hes1 has a role for the correct fusion of the two anlages at E13.5. At E16.5, Hes1 is involved in normal endocrine function in differentiated thyrocytes and C-cells.
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pone-0016752-g008: Proposed roles of Hes1 during murine thyroid development and function.Hes1 controls the number of thyrocyte progenitors in the median anlage (in grey) at E9.5 and C-cell progenitors in the ultimobranchial bodies (in white) at E11.5. Hes1 has a role for the correct fusion of the two anlages at E13.5. At E16.5, Hes1 is involved in normal endocrine function in differentiated thyrocytes and C-cells.

Mentions: Hes1 is well known in development of different tissues, particularly endoderm derived endocrine organs like pancreas, and neuroendocrine cells of lung. Hes1 controls normal development by regulating proliferation and differentiation and so cell fate. In mutant Hes1 mouse embryos, we found that the thyroid gland was hypoplastic and hypofunctional. Thus, the thyroid gland is not the first example of an endodermic tissue affected by Hes1. This study allowed us to involve a new gene in thyroid development (Figure 8). However, specification of the median anlage and the ultimobranchial bodies was independent of Hes1.


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)

Proposed roles of Hes1 during murine thyroid development and function.Hes1 controls the number of thyrocyte progenitors in the median anlage (in grey) at E9.5 and C-cell progenitors in the ultimobranchial bodies (in white) at E11.5. Hes1 has a role for the correct fusion of the two anlages at E13.5. At E16.5, Hes1 is involved in normal endocrine function in differentiated thyrocytes and C-cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0016752-g008: Proposed roles of Hes1 during murine thyroid development and function.Hes1 controls the number of thyrocyte progenitors in the median anlage (in grey) at E9.5 and C-cell progenitors in the ultimobranchial bodies (in white) at E11.5. Hes1 has a role for the correct fusion of the two anlages at E13.5. At E16.5, Hes1 is involved in normal endocrine function in differentiated thyrocytes and C-cells.
Mentions: Hes1 is well known in development of different tissues, particularly endoderm derived endocrine organs like pancreas, and neuroendocrine cells of lung. Hes1 controls normal development by regulating proliferation and differentiation and so cell fate. In mutant Hes1 mouse embryos, we found that the thyroid gland was hypoplastic and hypofunctional. Thus, the thyroid gland is not the first example of an endodermic tissue affected by Hes1. This study allowed us to involve a new gene in thyroid development (Figure 8). However, specification of the median anlage and the ultimobranchial bodies was independent of Hes1.

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, Université 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