Altered forebrain and hindbrain development in mice mutant for the Gsh-2 homeobox gene
Altered forebrain and hindbrain development in mice mutant for the Gsh-2 homeobox gene
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DOI：
10.1006/dbio.1997.8733
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发表时间：
1997-11-15
影响因子：
2.7
通讯作者：
Potter, SS
中科院分区：
文献类型：
--
作者：
Szucsik, JC;Witte, DP;Potter, SS
哺乳动物大脑的模式化是由大量的调控基因组成的。在这里，我们研究的GSH-2非簇同源异型盒基因的发育功能。整体安装和连续切片原位杂交已被用来更好地确定GSH-2的表达领域内的发展前脑，中脑，和后脑。谷胱甘肽-2转录被证明是特别丰富的后脑和内的前脑神经节隆起的发展。此外，已经产生并表征了携带Gsh-e靶向突变的小鼠。纯合子突变体在出生后均不能存活超过1天。在生理水平上，突变体经历了呼吸暂停和血红蛋白氧合水平降低。在组织学上，突变体的大脑有显著的离散成分改变。在前脑的外侧神经节隆起的大小减少。在后脑，最后区，一个重要的心肺化学感受中心，缺席。邻近的孤束核，参与整合感觉输入，以维持稳态，也严重畸形的突变体。免疫组织化学被用来检查突变的大脑中的变化，特异性标记物的分布，肾上腺素能和胆碱能神经元。此外，原位杂交被用来定义的Dir 2和Nkx 2.1同源框基因在GSH-2突变小鼠的表达模式。突变的外侧神经节隆起显示异常缺乏Dir 2的表达。这些结果更好地定义了哺乳动物大脑发育的遗传程序，支持大脑发育的神经元模型，并进一步表明同源异型盒基因在遗传多样性生物体中具有相似的模式功能。(C)北京：科学出版社.
The patterning of the mammalian brain is orchestrated by a large battery of regulatory genes. Here we examine the developmental function of the Gsh-2 nonclustered homeobox gene. Whole-mount and serial section in situ hybridizations have been used to better define Gsh-2 expression domains within the developing forebrain, midbrain, and hindbrain. Gsh-2 transcripts are shown to be particularly abundant in the hindbrain and within the developing ganglionic eminences of the forebrain. In addition, mice carrying a targeted mutation of Gsh-e have been generated and characterized. Homozygous mutants uniformly failed to survive more than 1 day following birth. At the physiologic level the mutants experienced apnea and reduced levels of hemoglobin oxygenation. Histologically, the mutant brains had striking alterations of discrete components. In the forebrain the lateral ganglionic eminence was reduced in size. In the hindbrain, the area postrema, an important cardiorespiratory chemosensory center, was absent. The contiguous nucleus tractus solitarius, involved in integrating sensory input to maintain homeostasis, was also severely malformed in mutants. Immunohistochemistry was used to examine the mutant brains for alterations in the distribution of markers specific for serotonergic and cholinergic neurons. In addition, in situ hybridizations were used to define expression patterns of the Dir 2 and Nkx 2.1 homeobox genes in Gsh-2 mutant mice. The mutant lateral ganglionic eminences showed an abnormal absence of Dir 2 expression. These results better define the genetic program of development of the mammalian brain, support neuromeric models of brain development, and further suggest similar patterning function for homeobox genes in phylogenetically diverse organisms. (C) 1997 Academic Press.