An emerging role for prdm family genes in dorsoventral patterning of the vertebrate nervous system.
An emerging role for prdm family genes in dorsoventral patterning of the vertebrate nervous system.
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DOI：
10.1186/s13064-015-0052-8
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发表时间：
2015-10-24
影响因子：
3.6
通讯作者：
Sagerström CG
中科院分区：
文献类型：
--
作者：
Zannino DA;Sagerström CG
胚胎脊椎动物神经管沿背腹轴分为11个分子离散的祖结构域。这些结构域中的每一个都产生不同的神经元细胞类型；最腹侧的6个脑域负责运动回路，而背侧的5个脑域负责感觉回路。在最初的神经发生步骤之后，这些区域也会产生胶质细胞类型——星形胶质细胞或少突胶质细胞。这种DV模式是由两种形态因子——脊索和底板释放的sonic Hedgehog和顶板产生的Bone Morphogenetic Protein发起的，它们以浓度梯度的方式诱导DV轴上基因的表达。随后，这些dv限制基因合作定义祖细胞结构域，并控制每个结构域的神经元细胞命运规范和分化。参与这一过程的许多基因已被确定，但我们对潜在遗传程序的理解仍存在重大差距。在这里，我们回顾了最近的工作，确定了Prdm基因家族成员作为神经管DV模式的新调节器。许多Prdm蛋白通过控制组蛋白修饰来调节转录（要么通过内在组蛋白甲基转移酶活性，要么通过募集组蛋白修饰酶）。Prdm基因在沿神经管DV轴的空间受限结构域中表达，在祖结构域的规范以及运动神经元和各种类型中间神经元的后续分化中发挥重要作用。引人注目的是，Prdm蛋白似乎通过与其他转录因子（尤其是bHLH蛋白）结合并调节其活性来发挥作用。神经管DV模式中的关键转录因子的身份先前已经阐明（例如nkx， bHLH和pax家族），但现在似乎还需要一个额外的家族，并且它以一种潜在的新方式起作用。
The embryonic vertebrate neural tube is divided along its dorsoventral (DV) axis into eleven molecularly discrete progenitor domains. Each of these domains gives rise to distinct neuronal cell types; the ventral-most six domains contribute to motor circuits, while the five dorsal domains contribute to sensory circuits. Following the initial neurogenesis step, these domains also generate glial cell types—either astrocytes or oligodendrocytes. This DV pattern is initiated by two morphogens—Sonic Hedgehog released from notochord and floor plate and Bone Morphogenetic Protein produced in the roof plate—that act in concentration gradients to induce expression of genes along the DV axis. Subsequently, these DV-restricted genes cooperate to define progenitor domains and to control neuronal cell fate specification and differentiation in each domain. Many genes involved in this process have been identified, but significant gaps remain in our understanding of the underlying genetic program. Here we review recent work identifying members of the Prdm gene family as novel regulators of DV patterning in the neural tube. Many Prdm proteins regulate transcription by controlling histone modifications (either via intrinsic histone methyltransferase activity, or by recruiting histone modifying enzymes). Prdm genes are expressed in spatially restricted domains along the DV axis of the neural tube and play important roles in the specification of progenitor domains, as well as in the subsequent differentiation of motor neurons and various types of interneurons. Strikingly, Prdm proteins appear to function by binding to, and modulating the activity of, other transcription factors (particularly bHLH proteins). The identity of key transcription factors in DV patterning of the neural tube has been elucidated previously (e.g. the nkx, bHLH and pax families), but it now appears that an additional family is also required and that it acts in a potentially novel manner.