Retinoic acid regulates size, pattern and alignment of tissues at the head-trunk transition
Retinoic acid regulates size, pattern and alignment of tissues at the head-trunk transition
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DOI：
10.1242/dev.109603
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发表时间：
2014-11-01
期刊：
影响因子：
4.6
通讯作者：
Skromne, Isaac
中科院分区：
文献类型：
--
作者：
Lee, Keun;Skromne, Isaac
在头-躯干过渡处，后脑和脊髓与枕骨和椎骨对齐对于连贯的神经和骨骼系统组织至关重要。由区域的规格、图案或相对轴向位置缺陷引起的神经或中胚层组织构型的变化可严重损害其整合和功能。在这里，我们表明，协调神经和中胚层组织在斑马鱼头躯干过渡至关重要地依赖于两个新的活动的信号因子视黄酸（RA）：一个指定的大小和其他指定的轴向位置相对于中胚层结构的后脑领土。这些活动各自独立，但与RA在后脑模式中的既定功能相协调。使用神经和中胚层的地标，我们证明了RA在调整神经和中胚层组织的功能暂时先于后脑和脊髓领土的规范和HOX转录的激活。使用细胞移植试验，我们表明，RA在神经上皮细胞的活性调节后脑图案直接和领土大小规格间接。这种间接功能部分依赖于Wnt，但不依赖于FGF。重要的是，RA通过拮抗脊髓特异性基因cdx4的活性来指定和模式化后脑区域; cdx4的缺失挽救了与RA缺失相关的缺陷，包括后脑大小的减少和后菱形的丧失。我们建议，在头-躯干过渡，RA协调规范，图案化和对齐的神经和中胚层组织，是必不可少的组织和功能的神经和骨骼系统。
At the head-trunk transition, hindbrain and spinal cord alignment to occipital and vertebral bones is crucial for coherent neural and skeletal system organization. Changes in neural or mesodermal tissue configuration arising from defects in the specification, patterning or relative axial placement of territories can severely compromise their integration and function. Here, we show that coordination of neural and mesodermal tissue at the zebrafish head-trunk transition crucially depends on two novel activities of the signaling factor retinoic acid (RA): one specifying the size and the other specifying the axial position relative to mesodermal structures of the hindbrain territory. These activities are each independent but coordinated with the well-established function of RA in hindbrain patterning. Using neural and mesodermal landmarks we demonstrate that the functions of RA in aligning neural and mesodermal tissues temporally precede the specification of hindbrain and spinal cord territories and the activation of hox transcription. Using cell transplantation assays we show that RA activity in the neuroepithelium regulates hindbrain patterning directly and territory size specification indirectly. This indirect function is partially dependent on Wnts but independent of FGFs. Importantly, RA specifies and patterns the hindbrain territory by antagonizing the activity of the spinal cord specification gene cdx4; loss of Cdx4 rescues the defects associated with the loss of RA, including the reduction in hindbrain size and the loss of posterior rhombomeres. We propose that at the head-trunk transition, RA coordinates specification, patterning and alignment of neural and mesodermal tissues that are essential for the organization and function of the neural and skeletal systems.