Ectopic bone morphogenetic proteins 5 and 4 in the chicken forebrain lead to cyclopia and holoprosencephaly
Ectopic bone morphogenetic proteins 5 and 4 in the chicken forebrain lead to cyclopia and holoprosencephaly
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DOI：
10.1073/pnas.96.5.2439
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Grinspan, JB
中科院分区：
文献类型：
--
作者：
Golden, JA;Bracilovic, A;Grinspan, JB
在发育中的中枢神经系统中，正确的背腹模式需要来自神经管的背侧和腹侧部分的信号。来自多项研究的数据表明，骨形态发生蛋白（BMP）和Sonic hedgehog蛋白是分泌因子，分别调节尾神经管内的背侧和腹侧规格。在发育中的喙部中枢神经系统中，Sonic hedgehog蛋白也参与腹侧区域化;然而，BMP在发育中的大脑中的作用不太清楚。我们假设骨形成蛋白也在脊椎动物前脑的背侧特化中发挥作用。为了验证我们的假设，我们将浸泡在重组BMP 5或BMP 4中的珠子植入鸡前脑的神经管中。实验胚胎显示出基底端脑的损失，导致前脑无裂畸形（单个大脑半球）、独眼畸形（单个中线眼）和腹侧中线结构的损失。使用一组探针在背侧和腹侧前脑中表达的基因进行原位杂交，发现腹侧标记的丢失与背侧标记的维持。此外，我还发现，端脑基底部的缺失是细胞过度死亡的结果，而不是细胞命运的改变。这些数据提供的证据表明，BMP信号参与在体内发育的大脑的背腹图案，和背腹信号的干扰导致前脑的特定畸形。
Proper dorsal-ventral patterning in the developing central nervous system requires signals from both the dorsal and ventral, portions of the neural tube. Data from multiple studies have demonstrated that bone morphogenetic proteins (BMPs) and Sonic hedgehog protein are secreted factors that regulate dorsal and ventral specification, respectively, within the caudal neural tube. In the developing rostral central nervous system Sonic hedgehog protein also participates in ventral regionalization; however, the roles of BMPs in the developing brain are less clear. We hypothesized that BMPs also play a role in dorsal specification of the vertebrate forebrain. To test our hypothesis we implanted beads soaked in recombinant BMP5 or BMP4 into the neural tube of the chicken forebrain, Experimental embryos showed a loss of the basal telencephalon that resulted in holoprosencephaly (a single cerebral hemisphere), cyclopia (a single midline eye), and loss of ventral midline structures. In situ hybridization using a panel of probes to genes expressed in the dorsal and ventral forebrain revealed the loss of ventral markers with the maintenance of dorsal markers. Furthermore, me found that the loss of the basal telencephalon was the result of excessive cell death and not a change in cell fates. These data provide evidence that BMP signaling participates in dorsal-ventral patterning of the developing brain in vivo, and disturbances in dorsal-ventral signaling result in specific malformations of the forebrain.