Revealing the large-scale network organization of growth hormone-secreting cells

被引:130
作者
Bonnefont, X
Lacampagne, A
Sanchez-Hormigo, A
Fino, E
Creff, A
Mathieu, MN
Smallwood, S
Carmignac, D
Fontanaud, P
Travo, P
Alonso, G
Courtois-Coutry, N
Pincus, SM
Robinson, ICAF
Mollard, P [1 ]
机构
[1] Univ Montpellier I, CNRS, INSERM, Inst Funct Genom,U661,Unite Mixte Rech 5203,Dept, 141 Rue Cardonille, F-34094 Montpellier, France
[2] Univ Montpellier 2, CNRS, INSERM, Inst Funct Genom,U661,Unite Mixte Rech 5203,Dept, F-34094 Montpellier, France
[3] Ctr Hosp Univ Arnaud de Villeneuve, INSERM, U637, F-34295 Montpellier, France
[4] Natl Inst Med Res, Div Mol Neuroendocrinol, London NW7 1AA, England
[5] CNRS, Montpellier RIO Imaging, Ctr Rech Biochim Macromol, F-34293 Montpellier, France
关键词
biological rhythms; endocrinology; systems biology; connectivity; calcium;
D O I
10.1073/pnas.0508202102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pituitary growth hormone (GH)-secreting cells regulate growth and metabolism in animals and humans. To secrete highly ordered GH pulses (up to 1,000-fold rise in hormone levels in vivo), the pituitary GH cell population needs to mount coordinated responses to GH secretagogues, yet GH cells display an apparently heterogeneous scattered distribution in 2D histological studies. To address this paradox, we analyzed in 3D both positioning and signaling of GH cells using reconstructive, two-photon excitation microscopy to image the entire pituitary in GH-EGFP transgenic mice. Our results unveiled a homologous continuum of GH cells connected by adherens junctions that wired the whole gland and exhibited the three primary features of biological networks: robustness of architecture across lifespan, modularity correlated with pituitary GH contents and body growth, and connectivity with spatially stereotyped motifs of cell synchronization coordinating cell activity. These findings change our view of GH cells, from a collection of dispersed cells to a geometrically connected homotypic network of cells whose local morphology and connectivity can vary, to alter the timing of cellular responses to promote more coordinated pulsatile secretion. This large-scale 3D view of cell functioning provides a powerful approach to identify and understand other networks of endocrine cells that are thought to be scattered in situ. Many dispersed endocrine systems exhibit pulsatile outputs. We suggest that cell positioning and associated cell-cell connection mechanisms will be critical parameters that determine how well such systems can deliver a coordinated secretory pulse of hormone to their target tissues.
引用
收藏
页码:16880 / 16885
页数:6
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