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. 2017 Jul 13;7:5282. doi: 10.1038/s41598-017-05682-6

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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COUP-TFII ensures the appropriate morphogenesis and function of the hypothalamic-pituitary axis, especially the PVH nucleus, to prevent growth retardation. (A), The development of both posterior and anterior pituitary is abnormal in the newborn mutant. (Ag–i) White inserts in (Aa–f). (Am–r) Black inserts in (Aa–f). H&E staining showed that compared with the control (Aa,c,e,g,i,k), the posterior pituitary is shrunken along the rostro-caudal axis in the mutant at P0 (Ab,d,f,h,j,l). There are a few isolated blood cells in the anterior pituitary of the control (Am,o,q); however, many blood cell clusters, indicated by white arrow-heads, are observed in the mutant anterior pituitary (An,p,r). (B) The projection of AVP neuron to the posterior pituitary is abnormal in the mutant embryo at E15.5. Nissl staining images of the pituitary in the control (Ba,c) and the mutant at E15.5 (Bb,d). (Bc,d) Inserts in (Ba,b). The expression of AVP is readily detected in the control posterior pituitary at E15.5 (Be,g), but not in the mutant posterior pituitary (Bf,h). (C) A working model: during early development, COUP-TFII may activate or maintain the expression of Bdnf and Nrp1 genes to ensure the appropriate morphogenesis and function of the hypothalamic-pituitary axis, especially the PVH nucleus, and to prevent the growth failure. 3 V, third ventricle; A, anterior pituitary lobe; I, intermediate pituitary lobe; P, posterior pituitary lobe; PVH, paraventricular nucleus of hypothalamus. Scale bar, (Aa–f) 400 μm; (Ag–l) 200 μm; (Am–r) 100 μm; (Ba,b) 200 μm; (Bc–h) 100 μm.