Oliver G, Mailhos A, Wehr R, Copeland N G, Jenkins N A, Gruss P
Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Göttingen, Germany.
Development. 1995 Dec;121(12):4045-55. doi: 10.1242/dev.121.12.4045.
The Drosophila sine oculis homeobox-containing gene is known to play an essential role in controlling the initial events of pattern formation in the eye disc and is also required for the development of other parts of the fly visual system including the optic lobes. In this paper, we report the isolation of a sequence-related gene referred to as Six3. Based on its amino acid sequence, this gene can be included in the new Six/sine oculis subclass of homeobox genes. Early on, Six3 expression is restricted to the anterior neural plate including areas that later will give rise to ectodermal and neural derivatives. Later, once the longitudinal axis of the brain bends, Six3 mRNA is also found in structures derived from the anterior neural plate: ectoderm of nasal cavity, olfactory placode and Rathke's pouch, and also the ventral forebrain including the region of the optic recess, hypothalamus and optic vesicles. Based on this expression pattern, we conclude that Six3 is one of the most anterior homeobox gene reported to date. The high sequence similarity of Six3 with the Drosophila sine oculis, and its expression during eye development, suggests that this gene is the likely murine homologue. This finding supports the idea that mammals and insects share control genes such as eyeless/Pax6 (Halder, G., Callaerts, P. and Gehring, W. J. (1995) Science 267, 1788-1792), and also possibly other members of the regulatory cascade required for eye morphogenesis. In Small eye (Pax6) mouse mutants Six3 expression is not affected. Finally, based on the chromosomal localization and the expression pattern of the mouse Six3 gene, the human Six3 cognate could be a good candidate to be at least one of the genes affected in patients with holoprosencephaly type 2 due to an interstitial deletion of 2p21-p22. This region shares a homology with the distal region of mouse chromosome 17 where Six3 has been mapped.
已知果蝇含眼无同源框基因在控制眼盘模式形成的初始事件中起关键作用，并且果蝇视觉系统的其他部分（包括视叶）的发育也需要该基因。在本文中，我们报告了一个序列相关基因Six3的分离。基于其氨基酸序列，该基因可归入同源框基因的新Six/眼无亚类。早期，Six3的表达局限于前神经板，包括后来会产生外胚层和神经衍生物的区域。后来，一旦脑的纵轴弯曲，Six3 mRNA也出现在源自前神经板的结构中：鼻腔外胚层、嗅基板和拉特克囊，以及腹侧前脑，包括视隐窝、下丘脑和视泡区域。基于这种表达模式，我们得出结论，Six3是迄今为止报道的最靠前的同源框基因之一。Six3与果蝇眼无基因的高度序列相似性及其在眼发育过程中的表达表明，该基因可能是小鼠的同源物。这一发现支持了哺乳动物和昆虫共享诸如无眼/Pax6等控制基因的观点（Halder, G., Callaerts, P.和Gehring, W. J. (1995) Science 267, 1788 - 1792），并且也可能共享眼形态发生所需调控级联的其他成员。在小眼（Pax6）小鼠突变体中，Six3的表达不受影响。最后，基于小鼠Six3基因的染色体定位和表达模式，人类Six3同源物很可能是因2p21 - p22间质性缺失而导致的2型全前脑畸形患者中至少一个受影响基因的良好候选者。该区域与已定位Six3的小鼠17号染色体远端区域具有同源性。
