A caudorostral wave of RALDH2 conveys anteroposterior information to the cardiac field
A caudorostral wave of RALDH2 conveys anteroposterior information to the cardiac field
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DOI：
10.1242/dev.00750
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发表时间：
2003-11-01
期刊：
影响因子：
4.6
通讯作者：
Xavier-Neto, J
中科院分区：
文献类型：
--
作者：
Hochgreb, T;Linhares, VL;Xavier-Neto, J
前后极性的建立是心脏发生过程中最早的决定之一，在心脏和血管之间的耦合中起着重要作用。最近的研究表明，视黄酸（RA）在AP极性与心脏的通讯中起作用。我们利用胚胎培养，原位杂交，形态测定，命运映射和治疗RA泛拮抗剂BMS 493研究心脏前体细胞和RA信号之间的关系。我们描述了两个阶段的AP信号由RA，反映在RALDH 2的表达。第一阶段（HH 4 -7）的特征是窦房前体和表达RALDH 2的外侧中胚层之间的接近度增加。在这一阶段，RA信号是一致的扩散的形态从一个大的领域，而不是一个单一的热点。第二阶段（HH 7 -8）的特点是由一个领域的RALDH 2起源于一个动态的和进化保守的尾侧波模式在外侧中胚层的心脏前体的渐进环绕。在这个阶段，心脏AP图案由RA是一致的局部行动RA通过调节激活Raldh 2基因在胚胎域。用BMS 493的全身治疗改变了心脏命运图，使得在通常没有心室前体的区域中发现心室前体。局部应用BMS 493抑制左前外侧中胚层的心房分化。RALDH 2的尾侧波作为RA的内源性来源建立心脏AP命运的鉴定提供了一个有用的模型来接近脊椎动物胚胎赋予其器官轴向信息的机制。
Establishment of anteroposterior (AP) polarity is one of the earliest decisions in cardiogenesis and plays an important role in the coupling between heart and blood vessels. Recent research implicated retinoic acid (RA) in the communication of AP polarity to the heart. We utilized embryo culture, in situ hybridization, morphometry, fate mapping and treatment with the RA pan-antagonist BMS493 to investigate the relationship between cardiac precursors and RA signalling. We describe two phases of AP signalling by RA, reflected in RALDH2 expression. The first phase (HH4-7) is characterized by increasing proximity between sino-atrial precursors and the lateral mesoderm expressing RALDH2. In this phase, RA signalling is consistent with diffusion of the morphogen from a large field rather than a single hot spot. The second phase (HH7-8) is characterized by progressive encircling of cardiac precursors by a field of RALDH2 originating from a dynamic and evolutionary-conserved caudorostral wave pattern in the lateral mesoderm. At this phase, cardiac AP patterning by RA is consistent with localized action of RA by regulated activation of the Raldh2 gene within an embryonic domain. Systemic treatment with BMS493 altered the cardiac fate map such that ventricular precursors were found in areas normally devoid of them. Topical application of BMS493 inhibited atrial differentiation in left anterior lateral mesoderm. Identification of the caudorostral wave of RALDH2 as the endogenous source of RA establishing cardiac AP fates provides a useful model to approach the mechanisms whereby the vertebrate embryo confers axial information on its organs.