Brook F A, Shum A S, Van Straaten H W, Copp A J
Department of Zoology, University of Oxford, UK.
Development. 1991 Oct;113(2):671-8. doi: 10.1242/dev.113.2.671.
Delayed closure of the posterior neuropore (PNP) occurs to a variable extent in homozygous mutant curly tail (ct) mouse embryos, and results in the development of spinal neural tube defects (NTD) in 60% of embryos. Previous studies have suggested that curvature of the body axis may delay neural tube closure in the cranial region of the mouse embryo. In order to investigate the relationship between curvature and delayed PNP closure, we measured the extent of ventral curvature of the neuropore region in ct/ct embryos with normal or delayed PNP closure. The results show significantly greater curvature in ct/ct embryos with delayed PNP closure in vivo than in their normal littermates. Reopening of the posterior neuropore in non-mutant mouse embryos, to delay neuropore closure experimentally, did not increase ventral curvature, suggesting that increased curvature in ct/ct embryos is not likely to be a secondary effect of delayed PNP closure. Experimental prevention of ventral curvature in ct/ct embryos, brought about by implantation of an eyelash tip longitudinally into the hindgut lumen, ameliorated the delay in PNP closure. We propose, therefore, that increased ventral curvature of the neuropore region of ct/ct embryos imposes a mechanical stress, which opposes neurulation and thus delays closure of the PNP. Increased ventral curvature may arise as a result of a cell proliferation imbalance, which we demonstrated previously in affected ct/ct embryos.
纯合突变卷曲尾（ct）小鼠胚胎中后神经孔（PNP）延迟关闭的程度各不相同，60%的胚胎会出现脊髓神经管缺陷（NTD）。先前的研究表明，体轴弯曲可能会延迟小鼠胚胎颅部神经管的闭合。为了研究弯曲与PNP延迟关闭之间的关系，我们测量了PNP关闭正常或延迟的ct/ct胚胎神经孔区域腹侧弯曲的程度。结果显示，与正常同窝小鼠相比，体内PNP延迟关闭的ct/ct胚胎的弯曲程度明显更大。在非突变小鼠胚胎中重新打开后神经孔以实验性地延迟神经孔关闭，并未增加腹侧弯曲，这表明ct/ct胚胎中弯曲增加不太可能是PNP延迟关闭的继发效应。通过将睫毛尖端纵向植入后肠腔来实验性预防ct/ct胚胎的腹侧弯曲，改善了PNP关闭的延迟。因此，我们提出，ct/ct胚胎神经孔区域腹侧弯曲增加会施加机械应力，这会阻碍神经胚形成，从而延迟PNP的关闭。腹侧弯曲增加可能是由于细胞增殖失衡导致的，我们之前在受影响的ct/ct胚胎中已经证明了这一点。
