甲状腺系统的发生
所有脊椎动物甲状腺功能的形态学具有相同基础，滤泡结构贯穿脊椎动物进化的全过程。与此相反，甲状腺大体解剖在脊椎动物中各有不同。胎盘哺乳动物和一些爬行动物，甲状腺横跨气管，由中间峡部相连的两侧叶组成。在非胎盘哺乳动物、鸟类、两栖类动物中，甲状腺由两个独立侧叶组成。在软骨鱼类和一些硬骨鱼类（主要是海洋鱼类）中，甲状腺集中在一致密器官中。其余的海洋鱼类和大部分淡水硬骨鱼类中，甲状腺由分散在咽下结缔组织中无被囊滤泡组成。常在这些动物的非咽部区域（如肾脏、心脏、食管或脾）发现异位滤泡。所有脊椎动物的甲状腺形态发生过程中都按照相同途径[49]，甲状腺原基从咽部始基处开始外翻，向尾部迁移，最终到达定义的甲状腺区域。
参考文献
[1] Trueba S S, Augé J, Mattei G, et al.PAX8, TITF1,and FOXE1 Gene Expression Patterns during Human Development: New Insights into Human Thyroid Development and Thyroid Dysgenesis-Associated Malformations[J].Journal of Clinical Endocrinology &Metabolism,2005,90(1):455.
[2] Parlato R, Rosica A, Rodriguezmallon A, et al.An integrated regulatory network controlling survival and migration in thyroid organogenesis[J].Developmental Biology, 2004,276(2):464-475.
[3] Kanaiazuma M, Kanai Y, Gad J M, et al.Depletion of definitive gut endoderm in Sox17-null mutant mice[J].Development, 2002,129(10):2367-2379.
[4] Lammert E, Cleaver O, Melton D.Role of endothelial cells in early pancreas and liver development[J].Mechanisms of Development, 2003,120(1):59-64.
[5] Fagman H, Liao J, Westerlund J, et al.The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning[J].Human Molecular Genetics, 2007,16(3):276.
[6] Felice M D, Ovitt C, Biffali E, et al.A mouse model for hereditary thyroid dysgenesis and cleft palate[J].Nature Genetics,1998,19(4):395.
[7] S S-T, A C, G S, et al.Molecular mechanisms of thyroid dysgenesis.%A Polak M[J].Hormone research,2004,null(undefined):14-21.
[8] Lazzaro D, Price M, De F M, et al.The transcription factor TTF1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain[J].Development, 1991,113(4):1093-1104.
[9] De F M, Postiglione M P, Di L R.Minireview: thyrotropin receptor signaling in development and differentiation of the thyroid gland: insights from mouse models and human diseases[J].Endocrinology,2004,145(9):4062-4067.
[10] Hilfer S R, Stern M.Instability of the epithelialmesenchymal interaction in the eight-day embryonic chick thyroid[J].Journal of Experimental Zoology Part A Ecological Genetics & Physiology,1971,178(3):293-305.
[11] Hick A C, Delmarcelle A S, Bouquet M, et al.Reciprocal epithelial:endothelial paracrine interactions during thyroid development govern follicular organization and C-cells differentiation[J].Developmental Biology,2013,381(1):227-240.
[12] Kameda Y, Nishimaki T, Chisaka O, et al.Expression of the epithelial marker E-cadherin by thyroid C cells and their precursors during murine development[J].Journal of Histochemistry & Cytochemistry, 2007,55(10):1075-1088.
[13] Kameda Y, Nishimaki T, M, Jiang S, et al.Mash1 regulates the development of C cells in mouse thyroid glands[J].Developmental Dynamics,2010,236(1):262-270.
[14] Kusakabe T, Hoshi N, Kimura S.Origin of the ultimobranchial body cyst: T/ebp/NKX2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid[J].Developmental Dynamics, 2006,235(5):1300-1309.
[15] Manley N R, Capecchi M R.The role of Hoxa-3 in mouse thymus and thyroid development[J].Development,1995,121(7):1989-2003.
[16] Thomas P Q, Brown A, Beddington R S.Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors[J].Development,1998,125(1):85-94.
[17] Felice M D, Lauro R D.Thyroid Development and Its Disorders: Genetics and Molecular Mechanisms[J].Endocrine Reviews,2004,25(5):722.
[18] R D L.Murine models for the study of thyroid gland development.%A De Felice M[J].Endocrine development,2007,10(undefined):1-14.
[19] Guazzi S, Price M, De F M, et al.Thyroid nuclear factor 1 (TTF1) contains a homeodomain and displays a novel DNA binding specificity[J].Embo Journal,1990,9(11):3631-3639.
[20] Lee B J, Cho G J, Jr N R, et al.TTF1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion[J].Molecular & Cellular Neuroscience, 2001,17(1):107-126.
[21] Kimura S, Hara Y, Pineau T, et al.The T/ebp null mouse:thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain,and pituitary[J].Genes Dev, 1996,10(1):60-69.
[22] Kusakabe T, Kawaguchi A, Hoshi N, et al.Thyroidspecific enhancer-binding protein/NKX2.1 is required for the maintenance of ordered architecture and function of the differentiated thyroid[J].Molecular Endocrinology,2006,20(8):1796-1809.
[23] Ngan ESW, Lang BHH, Liu T, et al.A Germline Mutation (A339V) in Thyroid Transcription Factor-1(TITF-1/NKX2.1) in Patients With Multinodular Goiter and Papillary Thyroid Carcinoma[J].J Natl Cancer Inst,2009,101(3):162-175.
[24] K C, C W, D S, et al.PAX8, a murine paired box gene expressed in the developing excretory system and thyroid gland.%A Plachov D[J].Development (Cambridge,England) , 1990,110(2):643-651.(https://www.daowen.com)
[25] Wistuba J, Mittag J, Luetjens C M, et al.Male congenital hypothyroid PAX8-/- mice are infertile despite adequate treatment with thyroid hormone[J].Journal of Endocrinology, 2007,192(1):99-109.
[26] Van R P, Vassart G, Christophe D.PAX8 expression in primary cultured dog thyrocyte is increased by cyclic AMP[J].Biochim Biophys Acta,1996,1307(1):97-103.
[27] JE N, A W B, M R E.PAX8 promotes tumor cell growth by transcriptionally regulating E2F1 and stabilizing RB protein.%A Li CG[J].Oncogene,2011,30(48):4824-4834.
[28] Ohno M, Zannini M, Levy O,et al.The paired-domain transcription factor PAX8 binds to the upstream enhancer of the rat sodium/iodide symporter gene and participates in both thyroid-specific and cyclic-AMP-dependent transcription[J].Molecular & Cellular Biology,1999,19(3):2051-2060.
[29] Magliano M P D, Lauro R D, Zannini M.PAX8 has a key role in thyroid cell differentiation[J].Proceedings of the National Academy of Sciences of the United States of America, 2000,97(24):13144-13149.
[30] De C T, Di P T, Fichera I, et al.An essential role for PAX8 in the transcriptional regulation of cadherin-16 in thyroid cells[J].Molecular Endocrinology, 2012,26(1):67-78.
[31] Zannini M, Avantaggiato V, Biffali E, et al.TTF2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role controlling the onset of differentiation[J].Embo Journal,2001,20(8):2108.
[32] Lai E, Prezioso V R, Tao W F, et al.Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head[J].Genes Dev,1991,5(3):416-427.
[33] Dathan N, Parlato R, Rosica A, et al.Distribution of the titf2/FOXE1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair[J].Developmental Dynamics, 2002,224(4):450-456.
[34] Castanet M, Polak M.Spectrum of Human FOXE1/TTF2 Mutations[J].Hormone Research in Paediatrics.2010,73(6):423-429.
[35] Bullock M, Duncan E L, O’Neill C, et al.Association of FOXE1 polyalanine repeat region with papillary thyroid cancer[J].Journal of Clinical Endocrinology &Metabolism, 2012,97(9):1814-1819.
[36] Sequeira M, Al-Khafaji F, Park S, et al.Production and application of polyclonal antibody to human thyroid transcription factor 2 reveals thyroid transcription factor 2 protein expression in adult thyroid and hair follicles and prepubertal testis[J].Thyroid,2003,13(10):927-932.
[37] Brancaccio A, Minichiello A, Grachtchouk M, et al.Requirement of the forkhead gene FOXE1, a target of sonic hedgehog signaling, in hair follicle morphogenesis[J].Human Molecular Genetics,2004,13(21):2595-2606.
[38] Postiglione M P, Parlato R, Rodriguez-Mallon A, et al.Role of the Thyroid-Stimulating Hormone Receptor Signaling in Development and Differentiation of the Thyroid Gland[J].Proceedings of the National Academy of Sciences of the United States of America,2002,99(24):15462-15467.
[39] Perrone L, Pasca dMM, Zannini M,et al.The thyroid transcription factor 2 (TTF2) is a promoterspecific DNA-binding independent transcriptional repressor[J].Biochemical & Biophysical Research Communications,2000,275(1):203.
[40] Martinez Barbera J P, Clements M, Thomas P, et al.The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation[J].Development,2000,127(11):2433.
[41] Elsalini O A, Gartzen J V, Cramer M, et al.Zebrafish HHEX, nk2.1a, and PAX2.1 regulate thyroid growth and differentiation downstream of Nodaldependent transcription factors[J].Developmental Biology,2003,263(1):67.
[42] Thomas W,Dejun A, Jeffrey J S, et al.Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals[J].Development, 2007,134(15):2871-2879.
[43] Puppin C, Presta I, D’Elia A V, et al.Functional interaction among thyroid-specific transcription factors:PAX8 regulates the activity of Hex promoter[J].Molecular& Cellular Endocrinology,2004,214(1):117-125.
[44] Maquet E, Costagliola S, Parma J, et al.Lethal respiratory failure and mild primary hypothyroidism in a term girl with a de novo heterozygous mutation in the TITF1/NKX2.1 gene[J].The Journal of clinical endocrinology and metabolism, 2009,94(1):197-203.
[45] Moya C M, Nanclares GPD, Casta O L, et al.Functional Study of a Novel Single Deletion in the TITF1/NKX2.1 Homeobox Gene That Produces Congenital Hypothyroidism and Benign Chorea But Not Pulmonary Distress[J].Journal of Clinical Endocrinology & Metabolism,2006,91(5):1832-1841.
[46] Carré A, Szinnai G, Castanet M, et al.Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome:rescue by PAX8 synergism in one case[J].Human Molecular Genetics, 2009,18(12):2266.
[47] P L, H K, MT P, et al.PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis.%A Macchia PE[J].Nature genetics,1998,19(1):83-86.
[48] Castanet M, Mallya U, Agostini M, et al.Maternal isodisomy for chromosome 9 causing homozygosity for a novel FOXE1 mutation in syndromic congenital hypothyroidism[J].The Journal of clinical endocrinology and metabolism,2010,95(8):4031-4036.
[49] Wendl T, Lun K, Mione M, et al.PAX2.1 is required for the development of thyroid follicles in zebrafish[J].Devel opment,2002,129(15):3751-3760.