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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.

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Thyroid morphology and expression of thyrocyte and C-cell markers at late embryonic stages.Staining for Nkx2-1 (A, B, F, G, K, L, P, Q), Pax8 and TG (C, H, M, R), CT and T4 (D, I, N, S), and Mash1 (E, J, O, T) at E16.5 (A–J) and E15.5 (K–T) in transverse sections from wild type and Hes1−/− mice. Boxed areas were enlarged (B–E, G–J, L–O, Q–T). Thyroid fusion was delayed by 3 days in Hes1−/− thyroids compared to wild type thyroids. tr: trachea; thy: thyroid; ma: median anlage; pt: parathyroid; UB: ultimobranchial body.
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pone-0016752-g003: Thyroid morphology and expression of thyrocyte and C-cell markers at late embryonic stages.Staining for Nkx2-1 (A, B, F, G, K, L, P, Q), Pax8 and TG (C, H, M, R), CT and T4 (D, I, N, S), and Mash1 (E, J, O, T) at E16.5 (A–J) and E15.5 (K–T) in transverse sections from wild type and Hes1−/− mice. Boxed areas were enlarged (B–E, G–J, L–O, Q–T). Thyroid fusion was delayed by 3 days in Hes1−/− thyroids compared to wild type thyroids. tr: trachea; thy: thyroid; ma: median anlage; pt: parathyroid; UB: ultimobranchial body.

Mentions: The wild type thyroid showed a high level of organisation at E16.5: Nkx2-1 was expressed in all thyroid cells, Pax8 in TG-producing thyrocytes organized in small thyroid follicles, and CT and Mash1 in C-cells scattered throughout the gland in a parafollicular position (Figure 3A–E). Mash1 expression was maintained in the developing thyroid, a finding at variance with results by Kameda et al. [16]. The Hes1−/− thyroid at E16.5 contained Nkx2-1-, Pax8-, TG-, and T4-expressing cells scattered throughout the gland (Figure 3F–I). Unexpectedly, we found that CT- and Mash1-expressing cells were clustered in a specific region of the gland (Figure 3I–J). We sought an explanation to this difference with the wild type gland by examining thyroids at two earlier stages, E15.5 (Figure 3K–T) and E13.5 (data not shown). At E15.5, fusion of the ultimobranchial bodies with the median anlage was apparent in wild type mice but not in Hes1−/− mice (n = 3) (Figure 3K, L, P, Q). The E15.5 ultimobranchial bodies of the Hes1−/− mice expressed a moderate number of Pax8-positive cells and few CT- and Mash1-positive cells (Figure 3R, S, T). Thus, absence of Hes1 was associated with a 3-day delay in the fusion of the ultimobranchial bodies to the median anlage: fusion occurred at E16.5 in the Hes1−/− mice and at E13.5 in the wild type mice. Moreover, CT- and Mash1-expressing cells in Hes1−/− thyroids had not spread throughout the gland at E16.5 due to delayed fusion of the ultimobranchial bodies with the median anlage. At this stage, CT- and Mash1-expressing cells were localized at the cranial part of the thyroid lobes.


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)

Thyroid morphology and expression of thyrocyte and C-cell markers at late embryonic stages.Staining for Nkx2-1 (A, B, F, G, K, L, P, Q), Pax8 and TG (C, H, M, R), CT and T4 (D, I, N, S), and Mash1 (E, J, O, T) at E16.5 (A–J) and E15.5 (K–T) in transverse sections from wild type and Hes1−/− mice. Boxed areas were enlarged (B–E, G–J, L–O, Q–T). Thyroid fusion was delayed by 3 days in Hes1−/− thyroids compared to wild type thyroids. tr: trachea; thy: thyroid; ma: median anlage; pt: parathyroid; UB: ultimobranchial body.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3045378&req=5

pone-0016752-g003: Thyroid morphology and expression of thyrocyte and C-cell markers at late embryonic stages.Staining for Nkx2-1 (A, B, F, G, K, L, P, Q), Pax8 and TG (C, H, M, R), CT and T4 (D, I, N, S), and Mash1 (E, J, O, T) at E16.5 (A–J) and E15.5 (K–T) in transverse sections from wild type and Hes1−/− mice. Boxed areas were enlarged (B–E, G–J, L–O, Q–T). Thyroid fusion was delayed by 3 days in Hes1−/− thyroids compared to wild type thyroids. tr: trachea; thy: thyroid; ma: median anlage; pt: parathyroid; UB: ultimobranchial body.
Mentions: The wild type thyroid showed a high level of organisation at E16.5: Nkx2-1 was expressed in all thyroid cells, Pax8 in TG-producing thyrocytes organized in small thyroid follicles, and CT and Mash1 in C-cells scattered throughout the gland in a parafollicular position (Figure 3A–E). Mash1 expression was maintained in the developing thyroid, a finding at variance with results by Kameda et al. [16]. The Hes1−/− thyroid at E16.5 contained Nkx2-1-, Pax8-, TG-, and T4-expressing cells scattered throughout the gland (Figure 3F–I). Unexpectedly, we found that CT- and Mash1-expressing cells were clustered in a specific region of the gland (Figure 3I–J). We sought an explanation to this difference with the wild type gland by examining thyroids at two earlier stages, E15.5 (Figure 3K–T) and E13.5 (data not shown). At E15.5, fusion of the ultimobranchial bodies with the median anlage was apparent in wild type mice but not in Hes1−/− mice (n = 3) (Figure 3K, L, P, Q). The E15.5 ultimobranchial bodies of the Hes1−/− mice expressed a moderate number of Pax8-positive cells and few CT- and Mash1-positive cells (Figure 3R, S, T). Thus, absence of Hes1 was associated with a 3-day delay in the fusion of the ultimobranchial bodies to the median anlage: fusion occurred at E16.5 in the Hes1−/− mice and at E13.5 in the wild type mice. Moreover, CT- and Mash1-expressing cells in Hes1−/− thyroids had not spread throughout the gland at E16.5 due to delayed fusion of the ultimobranchial bodies with the median anlage. At this stage, CT- and Mash1-expressing cells were localized at the cranial part of the thyroid lobes.

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
Related in: MedlinePlus