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Hes1 is required for the development of pharyngeal organs and survival of neural crest-derived mesenchymal cells in pharyngeal arches

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Abstract

Hes genes are required to maintain diverse progenitor cell populations during embryonic development. Loss of Hes1 results in a spectrum of malformations of pharyngeal endoderm-derived organs, including the ultimobranchial body (progenitor of C cells), parathyroid, thymus and thyroid glands, together with highly penetrant C-cell aplasia (81%) and parathyroid aplasia (28%). The hypoplastic parathyroid and thymus are mostly located around the pharyngeal cavity, even at embryonic day (E) 15.5 to E18.5, indicating the failure of migration of the organs. To clarify the relationship between these phenotypes and neural crest cells, we examine fate mapping of neural crest cells colonized in pharyngeal arches in Hes1 null mutants by using the Wnt1-Cre/R26R reporter system. In null mutants, the number of neural crest cells labeled by X-gal staining is markedly decreased in the pharyngeal mesenchyme at E12.5 when the primordia of the thymus, parathyroid and ultimobranchial body migrate toward their destinations. Furthermore, phospho-Histone-H3-positive proliferating cells are reduced in number in the pharyngeal mesenchyme at this stage. Our data indicate that the development of pharyngeal organs and survival of neural-crest-derived mesenchyme in pharyngeal arches are critically dependent on Hes1. We propose that the defective survival of neural-crest-derived mesenchymal cells in pharyngeal arches directly or indirectly leads to deficiencies of pharyngeal organs.

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References

  • Abu-Issa R, Smyth G, Smoak I, Yamamura K, Meyers EN (2002) Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse. Development 129:4613–4625

    PubMed  CAS  Google Scholar 

  • Akimoto M, Nishimaki T, Arai Y, Uchinuma E, Yamauchi H, Kameda Y (2010a) Hes1 regulates formations of the hypophyseal pars tuberalis and the hypothalamus. Cell Tissue Res 340:509–521

    Article  PubMed  Google Scholar 

  • Akimoto M, Kameda Y, Arai Y, Miura M, Nishimaki T, Takeda A, Uchinuma E (2010b) Hes1 is required for the development of craniofacial structures derived from ectomesenchymal neural crest cells. J Craniofac Surg 21:1443–1449

    Article  PubMed  Google Scholar 

  • Alt B, Elsalini OA, Schrumpf P, Haufs N, Lawson ND, Schwabe GC, Mundlos S, Gruters A, Krude H, Rohr KB (2006) Arteries define the position of the thyroid gland during its developmental relocalisation. Development 133:3797–3804

    Article  PubMed  CAS  Google Scholar 

  • Bertrand N, Castro DS, Guillemot F (2002) Proneural genes and the specification of neural cell types. Nat Rev Neurosci 3:517–530

    Article  PubMed  CAS  Google Scholar 

  • Bockman DE, Kirby ML (1984) Dependence of thymus development on derivatives of the neural crest. Science 223:498–500

    Article  PubMed  CAS  Google Scholar 

  • Chai Y, Jiang X, Ito Y, Bringas P Jr, Han J, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127:1671–1679

    PubMed  CAS  Google Scholar 

  • Chisaka O, Kameda Y (2005) Hoxa3 regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice. Cell Tissue Res 320:77–89

    Article  PubMed  CAS  Google Scholar 

  • Conway SJ, Henderson DJ, Copp AJ (1997) Pax3 is required for cardiac neural crest migration in the mouse: evidence from the splotch (Sp2H) mutant. Development 124:505–514

    PubMed  CAS  Google Scholar 

  • Cooley MA, Kern CB, Fresco VM, Wessels A, Thompson RP, McQuinn TC, Twal WO, Mjaatvedt CH, Drake CJ, Argraves WS (2008) Fibulin-1 is required for mophogenesis of neural crest-derived structures. Dev Biol 319:336–345

    Article  PubMed  CAS  Google Scholar 

  • Frank DU, Fotheringham LK, Brewer JA, Muglia LJ, Tristani-Firouzi M, Capecchi MR, Moon AM (2002) An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome. Development 129:4591–4603

    PubMed  CAS  Google Scholar 

  • Franz T (1989) Persistent truncus arterious in the splotch mutant mouse. Anat Embryol 180:457–464

    Article  PubMed  CAS  Google Scholar 

  • Graham A (2003) Development of the pharyngeal arches. Am J Med Gen 119A:251–256

    Article  Google Scholar 

  • Hadari YR, Gotoh N, Kouhara H, Lax I, Schlessinger J (2001) Critical role for the docking-protein FRS2α in FGF receptor-mediated signal transduction pathways. Proc Natl Acad Sci USA 98:8578–8583

    Article  PubMed  CAS  Google Scholar 

  • Hutson MR, Kirby ML (2003) Neural crest and cardiovascular development: a 20-year perspective. Birth Defects Res (Part C) 69:2–13

    Article  CAS  Google Scholar 

  • Ishibashi M, Ang SL, Shiota K, Nakanishi S, Kageyama R, Guillemot F (1995) Targeted disruption of mammalian hairy and enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects. Genes Dev 9:3136–3148

    Article  PubMed  CAS  Google Scholar 

  • Ito T, Udaka N, Yazawa T, Okudera K, Hayashi H, Sudo T, Guillemot F, Kageyama R, Kitamura H (2000) Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Development 127:3913–3921

    PubMed  CAS  Google Scholar 

  • Jensen J, Pedersen EE, Galante P, Hald J, Heller S, Ishibashi M, Kageyama R, Guillemot F, Serup P, Madsen OD (2000) Control of endodermal endocrine development by Hes-1. Nat Gen 24:36–44

    Article  CAS  Google Scholar 

  • Jiang X, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cardiac neural crest. Development 127:1607–1616

    PubMed  CAS  Google Scholar 

  • Kageyama R, Ohtsuka T (1999) The Notch-Hes pathway in mammalian neural development. Cell Res 9:179–188

    Article  PubMed  CAS  Google Scholar 

  • Kageyama R, Ohtsuka T, Kobayashi T (2008) Roles of Hes genes in neuronal development. Dev Growth Differ 50(Suppl 1):S97–S103

    Article  PubMed  CAS  Google Scholar 

  • Kameda Y (2007) Expression of glial progenitor markers p75NTR and S100 protein in the developing mouse parathyroid gland. Cell Tissue Res 327:15–23

    Article  PubMed  CAS  Google Scholar 

  • Kameda Y, Nishimaki T, Miura M, Jiang SX, Guillemot F (2007a) Mash1 regulates the development of C cells in mouse thyroid glands. Dev Dyn 236:262–270

    Article  PubMed  CAS  Google Scholar 

  • Kameda Y, Nishimaki T, Chisaka O, Iseki S, Sucov HM (2007b) Expression of the epithelial marker E-cadherin by thyroid C cells and their precursors during murine development. J Histochem Cytochem 55:1075–1088

    Article  PubMed  CAS  Google Scholar 

  • Kameda Y, Ito M, Nishimaki T, Gotoh N (2009) FRS2α is required for the separation, migration, and survival of pharyngeal-endoderm derived organs including thyroid, ultimobranchial body, parathyroid, and thymus. Dev Dyn 238:503–513

    Article  PubMed  Google Scholar 

  • Kameda Y, Saitoh T, Fujimura T (2011) Hes1 regulates the number and anterior-posterior patterning of mesencephalic dopaminergic neurons at the mid/hindbrain boundary (isthmus). Dev Biol 358:91–101

    Article  PubMed  CAS  Google Scholar 

  • Kusakabe Y, Miura H, Hashimoto R, Sugiyama C, Ninomiya Y, Hino A (2002) The neural differentiation gene Mash-1 has a distinct pattern of expression from the taste reception-related genes gustducin and T1R2 in the taste buds. Chem Senses 27:445–451

    Article  PubMed  CAS  Google Scholar 

  • Le Douarin NM, Kalcheim C (1999) The neural crest, 2nd edn. Cambridge University Press, Cambridge

    Book  Google Scholar 

  • Liu Z, Yu S, Manley NR (2007) Gcm2 is required for the differentiation and survival of parathyroid precursor cells in the parathyroid/thymus primordia. Dev Biol 305:333–346

    Article  PubMed  CAS  Google Scholar 

  • Minoux M, Rijli FM (2010) Molecular mechanisms of cranial neural crest cell migration and patterning in craniofacial development. Development 137:2605–2621

    Article  PubMed  CAS  Google Scholar 

  • Ota MS, Kaneko Y, Kondo K, Ogishima S, Tanaka H, Eto K, Kondo T (2009) Combined in silico and in vivo analyses reveal role of Hes1 in taste cell differentiation. PLoS Genet 5:e1000443

    Article  PubMed  Google Scholar 

  • Parlato R, Rosica A, Rodriguez-Mallon A, Affuso A, Postiglione MP, Arra C, Mansouri A, Kimura S, Di Lauro R, De Felice M (2004) An integrated regulatory network controlling survival and migration in thyroid organogenesis. Dev Biol 276:464–475

    Article  PubMed  CAS  Google Scholar 

  • Paylor R, Lindsay E (2006) Mouse models of 22q11 deletion syndrome. Biol Psychiatry 59:1172–1179

    Article  PubMed  CAS  Google Scholar 

  • Raetzman LT, Cai JX, Camper SA (2007) Hes1 is required for pituitary growth and melanotrope specification. Dev Biol 304:455–466

    Article  PubMed  CAS  Google Scholar 

  • Rochais F, Dandonneau M, Mesbah K, Jarry T, Mattei M-G, Kelly RG (2009) Hes1 is expressed in the second heart field and is required for outflow tract development. PLoS One 4:e6267

    Article  PubMed  Google Scholar 

  • Soriano P (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Gen 21:70–71

    Article  CAS  Google Scholar 

  • Suniara RK, Jenkinson EJ, Owen JJT (2000) An essential role for thymic mesenchyme in early T cell development. J Exp Med 191:1051–1056

    Article  PubMed  CAS  Google Scholar 

  • Tomita K, Hattori M, Nakamura E, Nakanishi S, Minato N, Kageyama R (1999) The bHLH gene Hes1 is essential for expansion of early T cell precursors. Genes Dev 13:1203–1210

    Article  PubMed  CAS  Google Scholar 

  • van Bueren KL, Papangeli I, Rochais F, Pearce K, Robert C, Calmont A, Szumska D, Kelly RG, Bhattacharya S, Scambler PJ (2010) Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome. Dev Biol 340:369–380

    Article  PubMed  Google Scholar 

  • Waldo KL, Lo CW, Kirby ML (1999) Connexin 43 expression reflects neural crest patterns during cardiovascular development. Dev Biol 208:307–323

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Nagy A, Larsson J, Dudas M, Sucov HM, Kaartinen V (2006) Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects. BMC Dev Biol 6:51

    Article  PubMed  Google Scholar 

  • Wurdak H, Ittner LM, Lang KS, Leveen P, Suter U, Fischer JA, Karlsson S, Born W, Sommer L (2005) Inactivation of TGFβ signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome. Genes Dev 19:530–535

    Article  PubMed  CAS  Google Scholar 

  • Zheng JL, Shou J, Guillemot F, Kageyama R, Gao WQ (2000) Hes1 is a negative regulator of inner ear hair cell differentiation. Development 127:4551–4560

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We thank Prof. Ryoichiro Kageyama (Institute for Virus Research, Kyoto University) for the gift of the Hes1 mouse line.

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Authors and Affiliations

  1. Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan

    Yoko Kameda

  2. Graduate school of Science, Kitasato University, Sagamihara, Kanagawa, 252-0374, Japan

    Takayoshi Saitoh

  3. Research Center for Biological Imaging, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan

    Noriko Nemoto & Tokio Katoh

  4. Molecular Craniofacial Embryology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Bunkyo-ku, Tokyo, 113-89549, Japan

    Sachiko Iseki

  5. Department of Dermatology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan

    Takao Fujimura

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  1. Yoko Kameda
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  2. Takayoshi Saitoh
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Correspondence to Yoko Kameda.

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Kameda, Y., Saitoh, T., Nemoto, N. et al. Hes1 is required for the development of pharyngeal organs and survival of neural crest-derived mesenchymal cells in pharyngeal arches. Cell Tissue Res 353, 9–25 (2013). https://doi.org/10.1007/s00441-013-1649-z

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  • DOI: https://doi.org/10.1007/s00441-013-1649-z

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