Abstract
Pituitary gland development is controlled by numerous signaling molecules, which are produced in the oral ectoderm and diencephalon. A newly described family of heparin-binding growth factors, namely midkine (MK)/pleiotrophin (PTN), is involved in regulating the growth and differentiation of many tissues and organs. Using in situ hybridization with digoxigenin-labeled cRNA probes, we detected cells expressing MK and PTN in the developing rat pituitary gland. At embryonic day 12.5 (E12.5), MK expression was localized in Rathke’s pouch (derived from the oral ectoderm) and in the neurohypophyseal bud (derived from the diencephalon). From E12.5 to E19.5, MK mRNA was expressed in the developing neurohypophysis, and expression gradually decreased in the developing adenohypophysis. To characterize MK-expressing cells, we performed double-staining of MK mRNA and anterior pituitary hormones. At E19.5, no MK-expressing cells were stained with any hormone. In contrast, PTN was expressed only in the neurohypophysis primordium during all embryonic stages. In situ hybridization clearly showed that MK was expressed in primitive (immature/undifferentiated) adenohypophyseal cells and neurohypophyseal cells, whereas PTN was expressed only in neurohypophyseal cells. Thus, MK and PTN might play roles as signaling molecules during pituitary development.
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We are grateful to David Kipler, ELS of Supernatant Communications, for revising the language of the manuscript.
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This work was partly supported by Grant-in-Aid for Young Scientists (B) (24790199) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by promotional funds for the Keirin Race of the Japan Keirin Association.
The authors have no conflict of interest that might prejudice the impartiality of this research.
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Fig. S1
MK expression in the pars tuberalis primordium at E14.5. In this high-magnification image of Fig. 2b, MK mRNA expression is negligible in the pars tuberalis primordium (double arrows in a). The region coincides with differentiating pituitary cells, which express αGSU (glycoprotein hormone α subunit) mRNA (b). Bar 100 μm (PDF 171 kb)
Fig. S2
In situ hybridization of MK and PTN in frontal sections at E15.5. MK mRNA expression is observed throughout the pars nervosa (PN), pars intermedia (PI), and pars distalis (PD, a). PTN mRNA signals are weak but widespread in the pars nervosa (b, III third ventricle). Bar 500 μm (PDF 190 kb)
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Fujiwara, K., Maliza, R., Tofrizal, A. et al. In situ hybridization analysis of the temporospatial expression of the midkine/pleiotrophin family in rat embryonic pituitary gland. Cell Tissue Res 357, 337–344 (2014). https://doi.org/10.1007/s00441-014-1875-z
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DOI: https://doi.org/10.1007/s00441-014-1875-z