Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development.
Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development.
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正常的垂体发展需要同型转录因子HESX1和SIX3之间的遗传相互作用。
DOI：
10.1016/j.ydbio.2008.08.008
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发表时间：
2008-12-15
影响因子：
2.7
通讯作者：
Martinez-Barbera, Juan Pedro
中科院分区：
文献类型：
--
作者：
Gaston-Massuet, Carles;Andoniadou, Cynthia L.;Signore, Massimo;Sajedi, Ezat;Bird, Sophie;Turner, James M. A.;Martinez-Barbera, Juan Pedro
Hesx1已被证明对正常的脑下垂体发育是必不可少的。同源异型盒基因Six3在小鼠发育过程中在发育中的脑垂体腺中表达，但由于在缺乏Six3基因的胚胎中脑垂体腺不被诱导，其在该组织中的功能已被排除在外。为了深入了解Six3在垂体发育过程中的作用，我们产生了Six3+/−；Hesx1Cre/+双杂合小鼠。引人注目的是，这些小鼠表现出明显的侏儒症，在断奶前后第一次被检测到，并在5-6周大时死亡。这些动物的甲状腺和性腺发育也受到损害。对Six3+/−；Hesx1Cre/+复合胚胎的分析表明，垂体功能低下可能是这些缺陷的原因，因为这些突变体的脑垂体发育严重受损。与Hesx1基因缺陷的胚胎相似，Rathke的囊袋最初在Six3+/−；Hesx1Cre/+复合胚胎中扩张，这是因为细胞增殖增加。随后，垂体前叶出现分叉、变形，偶尔在鼻咽腔内异位错位，但细胞分化未受影响。我们的研究揭示了Six3在正常脑垂体发育中的作用，这种作用在进化过程中可能是保守的，因为Six3也在人类胚胎的脑下垂体中表达。
Hesx1 has been shown to be essential for normal pituitary development. The homeobox gene Six3 is expressed in the developing pituitary gland during mouse development but its function in this tissue has been precluded by the fact that in the Six3-deficient embryos the pituitary gland is not induced. To gain insights into the function of Six3 during pituitary development we have generated Six3+/−; Hesx1Cre/+ double heterozygous mice. Strikingly, these mice show marked dwarfism, which is first detectable around weaning, and die by the 5th-6th week of age. Thyroid and gonad development is also impaired in these animals. Analysis of Six3+/−; Hesx1Cre/+ compound embryos indicates that hypopituitarism is the likely cause of these defects since pituitary development is severely impaired in these mutants. Similar to the Hesx1-deficient embryos, Rathke’s pouch is initially expanded in Six3+/−; Hesx1Cre/+ compound embryos due to an increase in cell proliferation. Subsequently, the anterior pituitary gland appears bifurcated, dysmorphic and occasionally ectopically misplaced in the nasopharyngeal cavity, but cell differentiation is unaffected. Our research has revealed a role for Six3 in normal pituitary development, which has likely been conserved during evolution as SIX3 is also expressed in the pituitary gland of the human embryo.
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影响因子：
4
作者：
Hoppler, Stefan;Kavanagh, Claire Louise
通讯作者：
Kavanagh, Claire Louise
影响因子：
4.8
作者：
GAGE, PJ;LOSSIE, AC;CAMPER, SA
通讯作者：
CAMPER, SA
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10.5
作者：
Dasen, JS;Barbera, JPM;Rosenfeld, MG
通讯作者：
Rosenfeld, MG
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30.8
作者：
Dattani, MT;Martinez-Barbera, JP;Robinson, ICAF
通讯作者：
Robinson, ICAF
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15.9
作者：
Kelberman, Daniel;Rizzoti, Karine;Dattani, Mehul T.
通讯作者：
Dattani, Mehul T.