Essential roles of Sall1 in kidney development
Essential roles of Sall1 in kidney development
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DOI：
10.1111/j.1523-1755.2005.00626.x
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发表时间：
2005-11-01
影响因子：
19.6
通讯作者：
Takasato, M
中科院分区：
文献类型：
--
作者：
Nishinakamura, R;Takasato, M
SALL 1是果蝇区域特异性同源异型基因spalt（sal）的哺乳动物同源物，人类SALL 1中的杂合突变导致Townes-Brocks综合征。我们分离了一个小鼠同源的SALL 1（Sall 1），并发现在Sall 1缺陷的小鼠死于围产期与肾脏发育不全。Sall 1在输尿管芽周围的后肾间充质中表达，并且Sall 1的纯合缺失导致不完全的输尿管芽生长。因此，Sall 1是输尿管芽侵入所必需的，输尿管芽是后肾发育的最初关键步骤。我们还产生了小鼠，其中绿色荧光蛋白（GFP）基因插入到Sall 1基因座，我们分离的GFP阳性群体从这些小鼠的胚胎肾荧光激活细胞分选（FACS）。然后，我们比较了基因表达谱的GFP阳性和阴性人口使用微阵列分析，然后通过原位杂交。我们检测到许多已知的基因是重要的后肾发育，基因表达丰富的后肾间充质。我们还发现了一些在后肾间充质中不表达的基因。因此，微阵列技术和Sall 1-GFP小鼠的组合是有用的系统性鉴定基因表达的发展中的肾脏。
SALL1 is a mammalian homologue of the Drosophila region-specific homeotic gene spalt (sal) and heterozygous mutations in SALL1 in humans lead to Townes-Brocks syndrome. We isolated a mouse homologue of SALL1 (Sall1) and found that mice deficient in Sall1 die in the perinatal period with kidney agenesis. Sall1 is expressed in the metanephric mesenchyme surrounding ureteric bud and homozygous deletion of Sall1 results in an incomplete ureteric bud outgrowth. Therefore, Sall1 is essential for ureteric bud invasion, the initial key step for metanephros development. We also generated mice in which a green fluorescent protein (GFP) gene was inserted into the Sall1 locus and we isolated the GFP-positive population from embryonic kidneys of these mice by fluorescence-activated cell sorting (FACS). We then compared gene expression profiles in the GFP-positive and -negative population using microarray analysis, followed by in situ hybridization. We detected many genes known to be important for metanephros development, and genes expressed abundantly in the metanephric mesenchyme. We also found groups of genes which are not known to be expressed in the metanephric mesenchyme. Thus a combination of microarray technology and Sall1-GFP mice is useful for systematic identification of genes expressed in the developing kidney.