Gonsar Ngawang, Coughlin Alicia, Clay-Wright Jessica A, Borg Bethanie R, Kindt Lexy M, Liang Jennifer O
Department of Biology, University of Minnesota Duluth, Duluth, MN.
Integrated Biosciences Graduate Program, University of Minnesota, Duluth, MN.
Genesis. 2016 Jan;54(1):3-18. doi: 10.1002/dvg.22908. Epub 2016 Jan 12.
Zebrafish with defective Nodal signaling have a phenotype analogous to the fatal human birth defect anencephaly, which is caused by an open anterior neural tube. Previous work in our laboratory found that anterior open neural tube phenotypes in Nodal signaling mutants were caused by lack of mesendodermal/mesodermal tissues. Defects in these mutants are already apparent at neural plate stage, before the neuroepithelium starts to fold into a tube. Consistent with this, we found that the requirement for Nodal signaling maps to mid-late blastula stages. This timing correlates with the timing of prechordal plate mesendoderm and anterior mesoderm induction, suggesting these tissues act to promote neurulation. To further identify tissues important for neurulation, we took advantage of the variable phenotypes in Nodal signaling-deficient sqt mutant and Lefty1-overexpressing embryos. Statistical analysis indicated a strong, positive correlation between a closed neural tube and presence of several mesendoderm/mesoderm-derived tissues (hatching glands, cephalic paraxial mesoderm, notochord, and head muscles). However, the neural tube was closed in a subset of embryos that lacked any one of these tissues. This suggests that several types of Nodal-induced mesendodermal/mesodermal precursors are competent to promote neurulation.
具有缺陷的Nodal信号通路的斑马鱼具有一种类似于致命的人类出生缺陷——无脑畸形的表型，无脑畸形是由前神经管开放引起的。我们实验室之前的研究发现，Nodal信号通路突变体中的前神经管开放表型是由于缺乏中内胚层/中胚层组织所致。在神经上皮开始折叠成神经管之前的神经板阶段，这些突变体中的缺陷就已经很明显了。与此一致的是，我们发现对Nodal信号通路的需求映射到囊胚中后期阶段。这个时间与脊索前板中内胚层和前中胚层诱导的时间相关，表明这些组织起到促进神经胚形成的作用。为了进一步确定对神经胚形成重要的组织，我们利用了Nodal信号缺陷的sqt突变体和过表达Lefty1的胚胎中的可变表型。统计分析表明，闭合的神经管与几种中内胚层/中胚层来源的组织（孵化腺、头侧轴旁中胚层、脊索和头部肌肉）的存在之间存在强烈的正相关。然而，在缺乏这些组织中的任何一种的一部分胚胎中，神经管是闭合的。这表明几种类型的由Nodal诱导的中内胚层/中胚层前体能够促进神经胚形成。
