Esterberg Robert, Delalande Jean-Marie, Fritz Andreas
Department of Biology, Emory University, Atlanta, GA 30322, USA.
Development. 2008 Dec;135(23):3891-901. doi: 10.1242/dev.029264. Epub 2008 Oct 23.
In zebrafish, BMP signaling establishes cell identity along the dorsoventral (DV) axis during gastrulation. Owing to the early requirements of BMP activity in DV patterning, it has been difficult to assign later roles in cell fate specification to specific BMP ligands. In this study, we have taken advantage of two follistatin-like genes (fstl1 and fstl2), as well as a transgenic zebrafish line carrying an inducible truncated form of the BMP-type 1 receptor to study the role of Bmp4 outside of the context of DV specification. Characterization of fstl1/2 suggests that they exert a redundant role as BMP antagonists during late gastrulation, regulating BMP activity in axial mesoderm. Maintenance of appropriate levels of BMP signaling is crucial for the proper development of chordamesoderm, a subset of axial mesoderm that gives rise to the notochord, but not prechordal mesoderm, which gives rise to the prechordal plate. Bmp4 activity in particular is required during a crucial window beginning at late gastrulation and lasting through early somitogenesis to promote chordamesoderm proliferation. In the absence of Bmp4, the notochord precursor pool is depleted, and the notochord differentiates prematurely. Our results illustrate a role for Bmp4 in the proliferation and timely differentiation of axial tissue after DV axis specification.
在斑马鱼中，骨形态发生蛋白（BMP）信号在原肠胚形成过程中沿背腹（DV）轴建立细胞身份。由于BMP活性在DV模式形成中的早期需求，很难将其在细胞命运特化中的后期作用归因于特定的BMP配体。在本研究中，我们利用了两个类卵泡抑素基因（fstl1和fstl2），以及一个携带可诱导的BMP 1型受体截短形式的转基因斑马鱼品系，来研究Bmp4在DV特化背景之外的作用。fstl1/2的特征表明，它们在原肠胚后期作为BMP拮抗剂发挥冗余作用，调节轴中胚层中的BMP活性。维持适当水平的BMP信号对于脊索中胚层的正常发育至关重要，脊索中胚层是轴中胚层的一个子集，可产生脊索，但不是前脊索中胚层，前脊索中胚层可产生前脊索板。特别是在从原肠胚后期开始并持续到早期体节形成的关键窗口期，需要Bmp4活性来促进脊索中胚层增殖。在没有Bmp4的情况下，脊索前体池会耗尽，并且脊索会过早分化。我们的结果说明了Bmp4在DV轴特化后轴组织的增殖和及时分化中的作用。
