Castranio Trisha, Mishina Yuji
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Dev Dyn. 2009 Jan;238(1):110-22. doi: 10.1002/dvdy.21829.
BMPs have been shown to play a role in neural tube development particularly as dorsalizing factors. To explore the possibility that BMP2 could play a role in the developing neural tube (NT) beyond the lethality of Bmp2 null embryos, we created Bmp2 chimeras from Bmp2 null ES cells and WT blastocysts. Analysis of Bmp2 chimeras reveals NT defects at day 9.5 (E9.5). We found that exclusion of Bmp2 null ES cells from the dorsal NT did not always prevent defects. For further comparison, we used a Bmp2 mutant line in a mixed background. Phenotypes observed were similar to chimeras including open NT defects, postneurulation defects, and abnormal neural ectoderm in heterozygous and homozygous null embryos demonstrating a pattern of dose-dependent signaling. Our data exposes BMP2 as a unique player in the developing NT for dorsal patterning and identity, and normal cephalic neural tube closure in a dose-dependent manner.
骨形态发生蛋白（BMPs）已被证明在神经管发育中发挥作用，尤其是作为背侧化因子。为了探索BMP2在发育中的神经管（NT）中可能发挥的作用，而不仅仅局限于Bmp2基因敲除胚胎的致死性，我们从Bmp2基因敲除的胚胎干细胞（ES细胞）和野生型囊胚中创建了Bmp2嵌合体。对Bmp2嵌合体的分析显示，在胚胎第9.5天（E9.5）出现神经管缺陷。我们发现，从神经管背侧排除Bmp2基因敲除的ES细胞并不总是能预防缺陷。为了进一步比较，我们使用了混合背景的Bmp2突变系。观察到的表型与嵌合体相似，包括神经管开放缺陷、神经胚形成后缺陷，以及杂合子和纯合子基因敲除胚胎中神经外胚层异常，这表明存在剂量依赖性信号传导模式。我们的数据表明，BMP2在发育中的神经管中是背侧模式形成和特征确定以及正常头侧神经管闭合的独特参与者，且呈剂量依赖性。
