Skip to main content
SpringerLink
Log in
Book cover

New Principles in Developmental Processes pp 97–108Cite as

Tbx1/Ripply3/Retinoic Acid Signal Network That Regulates Pharyngeal Arch Development

  • Chapter
  • First Online:

Abstract

The main feature of the developing pharynx of the vertebrate embryo is the transient appearance of a series of segmental pharyngeal arches. These arches are divided by internal pouches (endoderm) and external clefts (ectoderm) that together comprise the pharyngeal apparatus. The formation of the pharyngeal arches is essential for the development of many organs at later stages, and the pouches give rise to the rudiments of the thymus, parathyroid glands, and ultimobranchial body. During the development of the arches occur the sequential formation of pharyngeal arch arteries and the precise ingrowth of the axons of cranial nerves. Neural crest cells also migrate through each arch to differentiate in appropriate locations. Therefore, defects in pharyngeal arch development lead to deficits of pharyngeal arch arteries and mislocation or cell death of neural crest cells, which cause later malformations in the derivative organs. This chapter first overviews pharyngeal arch development, and then discusses our present knowledge regarding the genetic factors (Tbx1 and Ripply3) and signaling molecules (retinoic acid) that regulate the formation of the pharyngeal arches and their organ derivatives.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

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 (Camb) 129(19):4613–4625

    CAS  Google Scholar 

  • Arnold JS, Werling U, Braunstein EM, Liao J, Nowotschin S, Edelmann W, Hebert JM, Morrow BE (2006) Inactivation of Tbx1 in the pharyngeal endoderm results in 22q11DS malformations. Development (Camb) 133(5):977–987

    Article  CAS  Google Scholar 

  • Baker CV, Bronner-Fraser M (2001) Vertebrate cranial placodes. I. Embryonic induction. Dev Biol 232(1):1–61

    Article  CAS  PubMed  Google Scholar 

  • Baldini A (2005) Dissecting contiguous gene defects: TBX1. Curr Opin Genet Dev 15(3):279–284

    Article  CAS  PubMed  Google Scholar 

  • Duester G (2008) Retinoic acid synthesis and signaling during early organogenesis. Cell 134(6):921–931

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dupe V, Ghyselinck NB, Wendling O, Chambon P, Mark M (1999) Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse. Development (Camb) 126(22):5051–5059

    CAS  Google Scholar 

  • Fisher AL, Caudy M (1998) Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates. Genes Dev 12(13):1931–1940

    Article  CAS  PubMed  Google Scholar 

  • Foster K, Sheridan J, Veiga-Fernandes H, Roderick K, Pachnis V, Adams R, Blackburn C, Kioussis D, Coles M (2008) Contribution of neural crest-derived cells in the embryonic and adult thymus. J Immunol 180(5):3183–3189

    CAS  PubMed  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 (Camb) 129(19):4591–4603

    CAS  Google Scholar 

  • Gordon J, Manley NR (2011) Mechanisms of thymus organogenesis and morphogenesis. Development (Camb) 138(18):3865–3878

    Article  CAS  Google Scholar 

  • Graham A, Smith A (2001) Patterning the pharyngeal arches. Bioessays 23(1):54–61

    Article  CAS  PubMed  Google Scholar 

  • Hiruma T, Nakajima Y, Nakamura H (2002) Development of pharyngeal arch arteries in early mouse embryo. J Anat 201(1):15–29

    Article  PubMed Central  PubMed  Google Scholar 

  • Hu T, Yamagishi H, Maeda J, McAnally J, Yamagishi C, Srivastava D (2004) Tbx1 regulates fibroblast growth factors in the anterior heart field through a reinforcing autoregulatory loop involving forkhead transcription factors. Development (Camb) 131(21):5491–5502

    Article  CAS  Google Scholar 

  • Janesick A, Shiotsugu J, Taketani M, Blumberg B (2012) RIPPLY3 is a retinoic acid-inducible repressor required for setting the borders of the pre-placodal ectoderm. Development (Camb) 139(6):1213–1224

    Article  CAS  Google Scholar 

  • Jerome LA, Papaioannou VE (2001) DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet 27(3):286–291

    Article  CAS  PubMed  Google Scholar 

  • Jiang X, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cardiac neural crest. Development (Camb) 127(8):1607–1616

    CAS  Google Scholar 

  • Kaufman MH (1992) The atlas of mouse development. Academic, London, pp 131–133

    Google Scholar 

  • Kawamura A, Koshida S, Hijikata H, Ohbayashi A, Kondoh H, Takada S (2005) Groucho-associated transcriptional repressor ripply1 is required for proper transition from the presomitic mesoderm to somites. Dev Cell 9(6):735–744

    Article  CAS  PubMed  Google Scholar 

  • Kawamura A, Koshida S, Takada S (2008) Activator-to-repressor conversion of T-box transcription factors by the Ripply family of Groucho/TLE-associated mediators. Mol Cell Biol 28(10):3236–3244

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kirby ML, Waldo KL (1995) Neural crest and cardiovascular patterning. Circ Res 77(2):211–215

    Article  CAS  PubMed  Google Scholar 

  • Kobrynski LJ, Sullivan KE (2007) Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370(9596):1443–1452

    Article  CAS  PubMed  Google Scholar 

  • Kondow A, Hitachi K, Ikegame T, Asashima M (2006) Bowline, a novel protein localized to the presomitic mesoderm, interacts with Groucho/TLE in Xenopus. Int J Dev Biol 50(5):473–479

    CAS  PubMed  Google Scholar 

  • Kusakabe T, Hoshi N, Kimura S (2006) Origin of the ultimobranchial body cyst: T/ebp/Nkx2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid. Dev Dyn 235(5):1300–1309

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lindsay EA, Botta A, Jurecic V, Carattini-Rivera S, Cheah YC, Rosenblatt HM, Bradley A, Baldini A (1999) Congenital heart disease in mice deficient for the DiGeorge syndrome region. Nature (Lond) 401(6751):379–383

    CAS  Google Scholar 

  • Lindsay EA, Vitelli F, Su H, Morishima M, Huynh T, Pramparo T, Jurecic V, Ogunrinu G, Sutherland HF, Scambler PJ, Bradley A, Baldini A (2001) Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature (Lond) 410(6824):97–101

    Article  CAS  Google Scholar 

  • Maclean G, Dolle P, Petkovich M (2009) Genetic disruption of CYP26B1 severely affects development of neural crest derived head structures, but does not compromise hindbrain patterning. Dev Dyn 238(3):732–745

    Article  CAS  PubMed  Google Scholar 

  • Mark M, Ghyselinck NB, Chambon P (2004) Retinoic acid signalling in the development of branchial arches. Curr Opin Genet Dev 14(5):591–598

    Article  CAS  PubMed  Google Scholar 

  • Matt N, Ghyselinck NB, Wendling O, Chambon P, Mark M (2003) Retinoic acid-induced developmental defects are mediated by RARbeta/RXR heterodimers in the pharyngeal endoderm. Development (Camb) 130(10):2083–2093

    Article  CAS  Google Scholar 

  • Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, Xavier RJ, Demay MB, Russell RG, Factor S, Tokooya K, Jore BS, Lopez M, Pandita RK, Lia M, Carrion D, Xu H, Schorle H, Kobler JB, Scambler P, Wynshaw-Boris A, Skoultchi AI, Morrow BE, Kucherlapati R (2001) TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104(4):619–629

    Article  CAS  PubMed  Google Scholar 

  • Morimoto M, Sasaki N, Oginuma M, Kiso M, Igarashi K, Aizaki K, Kanno J, Saga Y (2007) The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite. Development (Camb) 134(8):1561–1569

    Article  CAS  Google Scholar 

  • Mulder GB, Manley N, Maggio-Price L (1998) Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1. Teratology 58(6):263–275

    Article  CAS  PubMed  Google Scholar 

  • Niederreither K, Subbarayan V, Dolle P, Chambon P (1999) Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nat Genet 21(4):444–448

    Article  CAS  PubMed  Google Scholar 

  • Niederreither K, Vermot J, Le Roux I, Schuhbaur B, Chambon P, Dolle P (2003) The regional pattern of retinoic acid synthesis by RALDH2 is essential for the development of posterior pharyngeal arches and the enteric nervous system. Development (Camb) 130(11):2525–2534

    Article  CAS  Google Scholar 

  • Okubo T, Kawamura A, Takahashi J, Yagi H, Morishima M, Matsuoka R, Takada S (2011) Ripply3, a Tbx1 repressor, is required for development of the pharyngeal apparatus and its derivatives in mice. Development (Camb) 138(2):339–348

    Article  CAS  Google Scholar 

  • Paschaki M, Schneider C, Rhinn M, Thibault-Carpentier C, Dembele D, Niederreither K, Dolle P (2013) Transcriptomic analysis of murine embryos lacking endogenous retinoic acid signaling. PLoS ONE 8(4):e62274

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Roberts C, Ivins S, Cook AC, Baldini A, Scambler PJ (2006) Cyp26 genes a1, b1, and c1 are down-regulated in Tbx1 null mice and inhibition of Cyp26 enzyme function produces a phenocopy of DiGeorge syndrome in the chick. Hum Mol Genet 15(23):3394–3410

    Article  CAS  PubMed  Google Scholar 

  • Scambler PJ (2010) 22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development. Pediatr Cardiol 31(3):378–390

    Article  PubMed  Google Scholar 

  • Takahashi J, Ohbayashi A, Oginuma M, Saito D, Mochizuki A, Saga Y, Takada S (2010) Analysis of Ripply1/2-deficient mouse embryos reveals a mechanism underlying the rostro-caudal patterning within a somite. Dev Biol 342(2):134–145

    Article  CAS  PubMed  Google Scholar 

  • Vermot J, Niederreither K, Garnier JM, Chambon P, Dolle P (2003) Decreased embryonic retinoic acid synthesis results in a DiGeorge syndrome phenotype in newborn mice. Proc Natl Acad Sci USA 100(4):1763–1768

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vitelli F, Morishima M, Taddei I, Lindsay EA, Baldini A (2002) Tbx1 mutation causes multiple cardiovascular defects and disrupts neural crest and cranial nerve migratory pathways. Hum Mol Genet 11(8):915–922

    Article  CAS  PubMed  Google Scholar 

  • Vitelli F, Huynh T, Baldini A (2009) Gain of function of Tbx1 affects pharyngeal and heart development in the mouse. Genesis 47(3):188–195

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wendling O, Dennefeld C, Chambon P, Mark M (2000) Retinoid signaling is essential for patterning the endoderm of the third and fourth pharyngeal arches. Development (Camb) 127(8):1553–1562

    CAS  Google Scholar 

  • Xu H, Cerrato F, Baldini A (2005) Timed mutation and cell-fate mapping reveal reiterated roles of Tbx1 during embryogenesis, and a crucial function during segmentation of the pharyngeal system via regulation of endoderm expansion. Development (Camb) 132(19):4387–4395

    Article  CAS  Google Scholar 

  • Zhang Z, Baldini A (2008) In vivo response to high-resolution variation of Tbx1 mRNA dosage. Hum Mol Genet 17(1):150–157

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Huynh T, Baldini A (2006) Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development (Camb) 133(18):3587–3595

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Animal Science, Kitasato University School of Medicine, Kanagawa, Japan

    Tadashi Okubo

Authors
  1. Tadashi Okubo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tadashi Okubo .

Editor information

Editors and Affiliations

  1. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

    Hisato Kondoh

  2. Graduate School Science, Nagoya University, Nagoya, Japan

    Atsushi Kuroiwa

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this chapter

Cite this chapter

Okubo, T. (2014). Tbx1/Ripply3/Retinoic Acid Signal Network That Regulates Pharyngeal Arch Development. In: Kondoh, H., Kuroiwa, A. (eds) New Principles in Developmental Processes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54634-4_8

Download citation

Publish with us

Policies and ethics

Search

Navigation