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PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are involved in vasculogenesis during rat embryonic pituitary development

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Abstract

We have recently shown that cells positive for the paired-related homeobox transcription factors PRRX1 and PRRX2 occur in the rat pituitary, and that they are derived from two different origins: pituitary-derived cells positive for stem cell marker SOX2 and extra-pituitary-derived cells negative for SOX2. In this study, we have further characterized the PRRX1- and PRRX2-positive cells that originate from extra-pituitary cells. Immunohistochemical analyses were performed with specific antibodies against PRRX1 and PRRX2 in order to clarify their roles in pituitary vasculogenesis. PRRX1- and PRRX2-positive cells were found in Atwell’s recess and at the periphery of the pituitary on embryonic day 15.5 (E15.5). Several PRRX1-positive cells then invaded the anterior lobe, together with a few PRRX2-positive cells, on E16.5. Some PRRX1-positive cells were also positive for mesenchymal stem cell marker NESTIN. Moreover, some PRRX1/NESTIN double-positive cells showed characteristics of vascular endothelial cells with an Isolectin-B4-binding capacity. PRRX1 co-localized with vascular smooth muscle cell/pericyte marker α-smooth muscle actin in the deep area of Atwell’s recess. We confirmed the presence of PRRX2/NESTIN double-positive cells at an entry area in Atwell’s recess and at the periphery of the pituitary, but PRRX2 did not co-localize with Isolectin B4 or α-smooth muscle actin. These data suggest that PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are present at the periphery of the embryonic pituitary and at the entry from Atwell’s recess and participate in pituitary vasculogenesis by differentiation into vascular endothelial cells and pericytes, whereas the presence of PRRX2 indicates much higher stemness than PRRX1.

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Abbreviations

PRRX1:

Paired-related homeobox 1

PRRX2:

Paired-related homeobox 2

SOX2:

Sex-determining region Y-box 2

DAPI:

4’6-diamidino-2-phenylindole

NESTIN:

Neuroepithelial stem cell

α-SMA:

α-Smooth muscle actin

FITC:

Fluorescein isothiocyanate

References

  • Balic A, Adams D, Mina M (2009) Prx1 and Prx2 cooperatively regulate the morphogenesis of the medial region of the mandibular process. Dev Dyn 238:2599–2613

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Boyd NL, Dhara SK, Rekaya R, Godbey EA, Hasneen K, Rao RR, West FD 3rd, Gerwe BA, Stice SL (2007) BMP4 promotes formation of primitive vascular networks in human embryonic stem cell-derived embryoid bodies. Exp Biol Med 232:833–843

    CAS  Google Scholar 

  • Brinkmeier ML, Davis SW, Carninci P, MacDonald JW, Kawai J, Ghosh D, Hayashizaki Y, Lyons RH, Camper SA (2009) Discovery of transcriptional regulators and signaling pathways in the developing pituitary gland by bioinformatic and genomic approaches. Genomics 93:449–460

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen J, Gremeaux L, Fu Q, Liekens D, Van Laere S, Vankelecom H (2009) Pituitary progenitor cells tracked down by side population dissection. Stem Cells 27:1182–1195

    Article  CAS  PubMed  Google Scholar 

  • Daikoku S, Kawano H, Abe K, Yoshinaga K (1981) Topographical appearance of adenohypophysial cells with special reference to the development of the portal system. Arch Histol Jpn 44:103–116

    Article  CAS  PubMed  Google Scholar 

  • Douville JM, Wigle JT (2007) Regulation and function of homeodomain proteins in the embryonic and adult vascular systems. Can J Physiol Pharmacol 85:55–65

    Article  CAS  PubMed  Google Scholar 

  • Fauquier T, Rizzoti K, Dattani M, Lovell-Badge R, Robinson IC (2008) SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland. Proc Natl Acad Sci U S A 105:2907–2912

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Herman IM, D’Amore PA (1985) Microvascular pericytes contain muscle and nonmuscle actins. J Cell Biol 101:43–53

    Article  CAS  PubMed  Google Scholar 

  • Higuchi M, Kato T, Chen M, Yako H, Yoshida S, Kanno N, Kato Y (2013) Temporospatial gene expression of Prx1 and Prx2 is involved in morphogenesis of cranial placode-derived tissues through epithelio-mesenchymal interaction during rat embryogenesis. Cell Tissue Res 353:27–40

    Article  CAS  PubMed  Google Scholar 

  • Higuchi M, Yoshida S, Ueharu H, Chen M, Kato T, Kato Y (2014) PRRX1 and PRRX2 distinctively participate in pituitary organogenesis and cell supply system. Cell Tissue Res 357:323–335

    Article  CAS  PubMed  Google Scholar 

  • Hunziker E, Stein M (2000) Nestin-expressing cells in the pancreatic islets of Langerhans. Biochem Biophys Res Commun 271:116–119

    Article  CAS  PubMed  Google Scholar 

  • Meijlink F, Beverdam A, Brouwer A, Oosterveen TC, Berge DT (1999) Vertebrate aristaless-related genes. Int J Dev Biol 43:651–663

    CAS  PubMed  Google Scholar 

  • Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN, Frenette PS (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829–834

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mitchell JM, Hicklin DM, Doughty PM, Hicklin JH, Dickert JWJ, Tolbert SM, Peterkova R, Kern MJ (2006) The Prx1 homeobox gene is critical for molar tooth morphogenesis. J Dent Res 85:888–893

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mitsuishi H, Kato T, Chen M, Cai LY, Yako H, Higuchi M, Yoshida S, Kanno N, Ueharu H, Kato Y (2013) Characterization of a pituitary-tumor-derived cell line, TtT/GF, that expresses Hoechst efflux ABC transporter subfamily G2 and stem cell antigen 1. Cell Tissue Res 354:563–572

    Article  CAS  PubMed  Google Scholar 

  • Shih CC, Weng Y, Mamelak A, LeBon T, Hu MC, Forman SJ (2001) Identification of a candidate human neurohematopoietic stem-cell population. Blood 98:2412–2422

    Article  CAS  PubMed  Google Scholar 

  • Skalli O, Pelte MF, Peclet MC, Gabbiani G, Gugliotta P, Bussolati G, Ravazzola M, Orci L (1989) Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes. J Histochem Cytochem 37:315–321

    Article  CAS  PubMed  Google Scholar 

  • Suga H, Kadoshima T, Minaguchi M, Ohgushi M, Soen M, Nakano T, Takata N, Wataya T, Muguruma K, Miyoshi H, Yonemura S, Oiso Y, Sasai Y (2011) Self-formation of functional adenohypophysis in three-dimensional culture. Nature 480:57–62

    Article  CAS  PubMed  Google Scholar 

  • Sunabori T, Tokunaga A, Nagai T, Sawamoto K, Okabe M, Miyawaki A, Matsuzaki Y, Miyata T, Okano H (2008) Cell-cycle-specific nestin expression coordinates with morphological changes in embryonic cortical neural progenitors. J Cell Sci 121:1204–1212

    Article  CAS  PubMed  Google Scholar 

  • Susa T, Kato T, Yoshida S, Yako H, Higuchi M, Kato Y (2012) Paired-related homeodomain proteins Prx1 and Prx2 are expressed in embryonic pituitary stem/progenitor cells and may be involved in the early stage of pituitary differentiation. J Neuroendocrinol 24:1201–1212

    Article  CAS  PubMed  Google Scholar 

  • Szabo K, Csanyi K (1982) The vascular architecture of the developing pituitary-median eminence complex in the rat. Cell Tissue Res 224:563–577

    Article  CAS  PubMed  Google Scholar 

  • Ueharu H, Higuchi M, Nishimura N, Yoshida S, Shibuya S, Sensui K, Kato T, Kato Y (2014) Expression of kruppel-like factor 6, KLF6, in rat pituitary stem/progenitor cells and its regulation of the PRRX2 gene. J Reprod Dev 60:304–311

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vankelecom H (2010) Pituitary stem/progenitor cells: embryonic players in the adult gland? Eur J Neurosci 32:2063–2081

    Article  PubMed  Google Scholar 

  • Vankelecom H, Gremeaux L (2010) Stem cells in the pituitary gland: a burgeoning field. Gen Comp Endocrinol 166:478–488

    Article  CAS  PubMed  Google Scholar 

  • Watkins-Chow DE, Camper SA (1998) How many homeobox genes does it take to make a pituitary gland? Trends Genet 14:284–290

    Article  CAS  PubMed  Google Scholar 

  • Yako H, Kato T, Yoshida S, Higuchi M, Chen M, Kanno N, Cai L-Y, Ueharu H, Kato Y (2013) Three-dimensional studies of Prop1-expressing cells in the rat pituitary just before birth. Cell Tissue Res 354:837–847

    Article  CAS  PubMed  Google Scholar 

  • Yoshida S, Kato T, Susa T, Cai L-Y, Nakayama M, Kato Y (2009) PROP1 coexists with SOX2 and induces PIT1-commitment cells. Biochem Biophys Res Commun 385:11–15

    Article  CAS  PubMed  Google Scholar 

  • Yoshida S, Kato T, Higuchi M, Yako H, Chen M, Kanno N, Ueharu H, Kato Y (2013) Rapid transition of NESTIN-expressing dividing cells from PROP1-positive to PIT1-positive advances prenatal pituitary development. J Neuroendocrinol 25:779–791

    Article  CAS  PubMed  Google Scholar 

  • Yoshida S, Higuchi M, Ueharu H, Nishimura N, Tsuda M, Nishihara H, Mitsuishi H, Kato T, Kato Y (2014) Characterization of murine pituitary-derived cell lines Tpit/F1, Tpit/E and TtT/GF. J Reprod Dev 60:295–303

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu X, Rosenfeld MG (2004) Transcriptional control of precursor proliferation in the early phases of pituitary development. Curr Opin Genet Dev 14:567–574

  • Zhu X, Gleiberman AS, Rosenfeld MG (2007) Molecular physiology of pituitary development: signaling and transcriptional networks. Physiol Rev 87:933–963

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Authors and Affiliations

  1. Organization for the Strategic Coordination of Research and Intellectual Property, Meiji University, Kanagawa, 214-8571, Japan

    Masashi Higuchi & Takako Kato

  2. Institute of Reproduction and Endocrinology, Meiji University, Kanagawa, 214-8571, Japan

    Masashi Higuchi, Takako Kato & Yukio Kato

  3. Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa, 214-8571, Japan

    Saishu Yoshida, Hiroki Ueharu & Naoto Nishimura

  4. Department of Life Science, School of Agriculture, Meiji University, Kanagawa, 214-8571, Japan

    Yukio Kato

Authors
  1. Masashi Higuchi
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  2. Takako Kato
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  3. Saishu Yoshida
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  4. Hiroki Ueharu
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  5. Naoto Nishimura
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  6. Yukio Kato
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Corresponding author

Correspondence to Yukio Kato.

Additional information

Masashi Higuchi and Takako Kato contributed equally to this work.

This work was partially supported by JSPS KAKENHI Grants nos. 21380184 to Y.K. and 24580435 to T.K., by a MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2014–2018, and by a research grant (A) to Y.K. from the Institute of Science and Technology, Meiji University. This study was also supported by the Meiji University International Institute for BioResource Research (MUIIR).

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Higuchi, M., Kato, T., Yoshida, S. et al. PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are involved in vasculogenesis during rat embryonic pituitary development. Cell Tissue Res 361, 557–565 (2015). https://doi.org/10.1007/s00441-015-2128-5

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  • DOI: https://doi.org/10.1007/s00441-015-2128-5

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