BMP-7 IS AN INDUCER OF NEPHROGENESIS, AND IS ALSO REQUIRED FOR EYE DEVELOPMENT AND SKELETAL PATTERNING

BMP-7 IS AN INDUCER OF NEPHROGENESIS, AND IS ALSO REQUIRED FOR EYE DEVELOPMENT AND SKELETAL PATTERNING
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DOI:
10.1101/gad.9.22.2808
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发表时间:
1995-11-15
影响因子:
10.5
通讯作者:
KARSENTY, G
KARSENTY, G
中科院分区:
生物学1区
文献类型:
--
作者:
LUO, G;HOFMANN, C;KARSENTY, G

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骨形态发生蛋白(BMPs)是一种多功能生长因子,最初因其诱导异位骨形成的能力而被发现。为了研究其中一种BMP-7的功能,我们使用胚胎干细胞技术产生了BMP-7缺陷小鼠。由于肾脏发育不良,缺乏bmp -7的小鼠在出生后不久死亡。对发育不同阶段的突变胚胎的组织学分析显示,后肾间充质细胞不能分化,导致新生肾脏肾小球的缺失。原位杂交分析显示,BMP-7的缺失影响了性后12.5 ~ 14.5天(dpc)肾形成分子标志物Pax-2和Wnt-4的表达。这表明BMP-7是肾形成的诱导剂。此外,bmp -7缺陷小鼠的眼睛缺陷似乎是在晶状体诱导过程中产生的。最后,缺乏bmp -7的小鼠也有局限于胸腔、头骨和后肢的骨骼模式缺陷。
Bone morphogenetic proteins (BMPs) are multifunctional growth factors originally identified by their ability to induce ectopic bone formation. To investigate the function of one of the BMPs, BMP-7, we have generated BMP-7-deficient mice using embryonic stem cell technology. BMP-7-deficient mice die shortly after birth because of poor kidney development. Histological analysis of mutant embryos at several stages of development revealed that metanephric mesenchymal cells fail to differentiate, resulting in a virtual absence of glomerulus in newborn kidneys. In situ hybridization analysis showed that the absence of BMP-7 affects the expression of molecular markers of nephrogenesis, such as Pax-2 and Wnt-4 between 12.5 and 14.5 days postcoitum (dpc). This identifies BMP-7 as an inducer of nephrogenesis. In addition, BMP-7-deficient mice have eye defects that appear to originate during lens induction. Finally, BMP-7-deficient mice also have skeletal patterning defects restricted to the rib cage, the skull, and the hindlimbs.