Abstract
Genetic disruption of Hoxa3 results in bilateral defects of the common carotid artery, which is derived from the third branchial arch artery. The tunica media of the great arteries derived from the arch arteries is formed by the ectomesenchymal neural crest cells. To examine the etiology of the regression of the third arch artery, we generated Hoxa3 homozygous null mutant embryos that expressed a lacZ marker transgene driven by a connexin43 (Cx43): promoter in the neural crest cells. The expression of β-galactosidase in these mouse embryos was examined by both whole-mount X-gal staining and immunohistochemistry with the monoclonal β-galactosidase antibody on sections. The migration of neural crest cells from the neural tube to the third branchial arch was not affected in the Hoxa3 homozygotes. The initial formation of the third arch artery was also not disturbed. The artery, however, regressed at embryonic day 11.5 (E11.5), when differentiation of the third pharyngeal arch began. The internal and external carotid arteries arose from the dorsal aorta in E12.5 null mutants, which showed an abnormal persistence of the ductus caroticus. The third pharyngeal arch of wild-type mice fuses with the fourth and second arches at E12.0. In the Hoxa3 null mutants, however, the fusion was delayed, and the hypoplastic third pharyngeal arch was still discerned at E12.5. Moreover, the number of proliferating cells in the third arch of the null mutants was small compared with that in the wild-type. Thus, Hoxa3 is required for the growth and differentiation of the third pharyngeal arch. The defective development of the third pharyngeal arch may induce the anomalies of the carotid artery system.
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References
Bockman D, Redmond ME, Waldo K, Davis H, Kirby MI (1987) Effect of neural crest ablation on development of the heart and arch arteries in the chick. Am J Anat 180:332–341
Chisaka O, Capecchi MR (1991) Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature 350:473–479
Clouthier DE, Williams SC, Yanagisawa H, Wieduwilt M, Richardson JA, Yanagisawa M (2000) Signaling pathways crucial for craniofacial development revealed by endothelin-A receptor-deficient mice. Dev Biol 217:10–24
Epstein JA, Li J, Lang D, Chen F, Brown CB, Jin F, Lu MM, Thomas M, Liu ECJ, Wessels A, Lo CW (2000) Migration of cardiac neural crest cells in Splotch embryos. Development 127:1869–1878
Francis-West P, Ladher R, Barlow A, Graveson A (1998) Signalling interactions during facial development. Mech Dev 75:3–28
Franz T (1989) Persistent truncus arterious in the splotch mutant mouse. Anat Embryol 180:457–464
Guris DL, Fantes J, Tara D, Druker BJ, Imamoto A (2001) Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nat Genet 27:293–298
Jerome LA, Papaioannou VE (2001) DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet 27:286–291
Jiang X, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cardiac neural crest. Development 127:1607–1616
Kameda Y, Miura M, Ohno S (1998) Localization and development of chromogranin A and luteinizing hormone immunoreactivities in the secretory-specific cells of the hypophyseal pars tuberalis of the chicken. Histochem Cell Biol 109:211–222
Kameda Y, Nishimaki T, Takeichi M, Chisaka O (2002) Homeobox gene Hoxa3 is essential for the formation of the carotid body in the mouse embryos. Dev Biol 247:197–209
Kameda Y, Watari-Goshima W, Nishimaki T, Chisaka O (2003) Disruption of the Hoxa3 homeobox gene results in anomalies of the carotid artery system and the arterial baroreceptors. Cell Tissue Res 311:343–352
Kameda Y, Arai Y, Nishimaki T, Chisaka O (2004) The role of Hoxa3 gene in parathyroid gland organogenesis of the mouse. J Histochem Cytochem 52:641–651
Kirby ML, Waldo KL (1995) Neural crest and cardiovascular patterning. Circ Res 77:211–215
Krumlauf R (1994) Hox genes in vertebrate development. Cell 78:191–201
Kurihara Y, Kurihara H, Oda H, Maemura K, Nagai R, Ishikawa T, Yazaki Y (1995) Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. J Clin Invest 96:293–300
Le Douarin NM, Kalcheim C (1999) The neural crest, 2nd edn. Cambridge University Press, Cambridge
Le Lièvre CS, Le Douarin NM (1975) Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos. J Embryol Exp Morphol 34:125–154
Li J, Chen F, Epstein JA (2000) Neural crest expression of Cre recombinase directed by the proximal Pax3 promoter in transgenic mice. Genesis 26:162–164
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 40:379–383
Lo CW, Cohen MF, Huang GY, Lazatin BO, Patel N, Sullivan R, Pauken C, Park SMJ (1997) Cx43 gap junction gene expression and gap junctional communication in mouse neural crest cells. Dev Genet 20:119–132
Manley NR, Capecchi MR (1995) The role of Hoxa-3 in mouse thymus and thyroid development. Development 121:1989–2003
Manzanares M, Cordes S, Ariza-McNaughton L, Sadl V, Maruthainar K, Barsh G, Krumlauf R (1999) Conserved and distinct roles of kreisler in regulation of the paralogous Hoxa3 and Hoxb3 genes. Development 126:759–769
Pietri T, Eder O, Blanche M, Thiery JP, Dufour S (2003) The human tissue plasminogen activator-Cre mouse: a new tool for targeting specifically neural crest cells and their derivatives in vivo. Dev Biol 259:176–187
Scambler PJ (2000) The 22q11 deletion syndromes. Hum Mol Genet 9:2421–2426
Shah NM, Groves AK, Anderson DJ (1996) Alternative neural crest cell fates are instructively promoted by TGFβ superfamily members. Cell 85:331–343
Shibuya M (2001) Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct 26:25–35
Thomas T, Kurihara H, Yamagishi H, Kurihara Y, Yazaki Y, Olson EN, Srivastava D (1998) A signaling cascade involving endothelin-1, dHAND and Msx1 regulates development of neural-crest-derived branchial arch mesenchyme. Development 125:3005–3014
Trainor PA, Krumlauf R (2000) Patterning the cranial neural crest: hindbrain segmentation and hox gene plasticity. Nature Rev 1:116–124
Waldo KL, Kumiski D, Kirby ML (1996) Cardiac neural crest is essential for the persistence rather than the formation of an arch artery. Dev Dyn 205:281–292
Waldo KL, Lo CW, Kirby ML (1999) Connexin 43 expression reflects neural crest patterns during cardiovascular development. Dev Biol 208:307–323
Watari N, Kameda Y, Takeichi M, Chisaka O (2001) Hoxa3 regulates integration of glossopharyngeal nerve precursor cells. Dev Biol 240:15–31
Yamauchi Y, Abe K, Mantani A, Hitoshi Y, Suzuki M, Osuzu F, Kuratani S, Yamamura K (1999) A novel transgenic technique that allows specific marking of the neural crest cell lineage in mice. Dev Biol 212:191–203
Yanagisawa H, Hammer RE, Richardson JA, Williams SC, Clouthier DE, Yanagisawa M (1998) Role of endothelin-1/endothelin-A receptor-mediated signaling pathway in the aortic arch patterning in mice. J Clin Invest 102:22–33
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We thank Mr. Toshiyuki Nishimaki and Mr. Shigeyoshi Maruyama for their excellent technical contributions.
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This work was supported in part by a grant (no. 14570026) from the Ministry of Education of Japan to Y.K.
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Chisaka, O., Kameda, Y. Hoxa3 regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice. Cell Tissue Res 320, 77–89 (2005). https://doi.org/10.1007/s00441-004-1042-z
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DOI: https://doi.org/10.1007/s00441-004-1042-z