Early mesencephalon/metencephalon patterning and development of the cerebellum.
Early mesencephalon/metencephalon patterning and development of the cerebellum.
复制标题
小脑的早期中脑/后脑模式和发育。
DOI：
--
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Joyner Al
中科院分区：
文献类型：
--
作者：
M. Wassef;Joyner Al
鸡的实验研究和小鼠突变体的分析为研究小脑原基的早期发育过程提供了一个框架。鸡的命运图谱研究表明，在早期阶段，小脑来自中脑和后脑（mes-met）的细胞。鸡的移植研究已经暗示了mes-met交界处（峡部）作为组织整个mes-met发育的分泌因子的来源，可能是通过刺激增殖和指定整个区域的位置值。Fgf-8被认为是峡部组织活动的主要因素。基因表达研究表明，同源异型盒基因Otx-2和Gbx-2的前部和后部表达域分别是大脑分裂的最早指示。此外，Otx-2/Gbx-2表达边界后来位于mes-met连接处。在小鼠中的遗传研究表明，Otx-2和Gbx-2是边界两侧细胞正常发育所必需的。此外，影响分泌因子Wnt-1（其在Otx-2/Gbx-2表达边界之前表达）和同源结构域转录因子Engrailed-1，2和Pax-2，5（其在mes-met中具有广泛的重叠表达结构域）的突变导致mes-met结构的缺失。总的来说，这些研究表明，小脑区域的具体化需要一个复杂的细胞和遗传相互作用的层次结构，这些层次结构逐渐将大脑细分为更小的区域。
Experimental studies in chick and analysis of mouse mutants have provided a framework for studying the early developmental processes involved in specifying the cerebellar anlage. Fate mapping studies in chick have shown that at early stages the cerebellum derives from cells in the mesencephalon and metencephalon (mes-met). Transplantation studies in chick have implicated the mes-met junction (isthmus) as a source of secreted factors that organize development of the entire mes-met, perhaps by stimulating proliferation and specifying positional values across the region. Fgf-8 has been implicated as a major factor involved in the isthmus organizing activity. Gene expression studies indicate that the anterior and posterior expression domains of the homeobox genes Otx-2 and Gbx-2, respectively, are the earliest indication of a division of the brain. Furthermore, the Otx-2/Gbx-2 expression border later resides at the mes-met junction. Genetic studies in mouse have shown that Otx-2 and Gbx-2 are required for normal development of cells on both sides of the border. In addition, mutations affecting the secreted factor Wnt-1, which is expressed anterior to the Otx-2/Gbx-2 expression border and the homeodomain transcription factors, Engrailed-1,2 and Pax-2,5 that have broad overlapping expression domains in the mes-met, result in deletions of mes-met structures. Taken together, these studies suggest that specification of the cerebellar territory requires a hierarchy of complex cellular and genetic interactions that gradually subdivide the brain into smaller regions.