Xenbase Image ID: 153584

Figure 5. Left–Right Determination in Fish and Frogs Studies in zebrafish and Xenopus have greatly contributed to our understanding of L/R development in vertebrates. Specifically, a variety of zebrafish mutants and surgical manipulations in Xenopus have been invaluable in demonstrating a key role for midline structures in L/R determination. It is becoming increasingly clear that the basic mechanisms and the molecular players are conserved among vertebrates, but interesting variations on the general L/R theme occur in fish and frogs. For example, in Xenopus (A), the L/R axis appears to develop significantly earlier than in other vertebrates. A “left–right coordinator” (LRC; in light blue), mediated by the activity of the TGF-β factor Vg1 ( 31 and 69), has been proposed to exist in the left side of the early blastula (at the 16-cell stage), establishing a mutual antagonism with a BMP activity in the right side (in light orange). The L/R coordinator would subsequently influence the Spemann organizer (depicted in black), which in turn relays the L/R positional information to other tissues. Interestingly, a transient array of microtubules during the first cell cycle appears to be essential for L/R development, suggesting that the L/R coordinator may be established as early as the D/V axis. Expression of Nodal (and, hence, Pitx2) can be induced by Vg1 and is antagonized by BMPs, which again stresses the conservation of the mechanism of control of Nodal and its targets. The midline is indicated in dark blue. (This figure has been adapted from Hyatt and Yost 1998 and Ramsdell and Yost 1999). Less is known about L/R development in the zebrafish embryo (B). None of the four hedgehog (hh) genes (Shh, twhh, ehh, and hhc) has been described to be asymmetrically expressed in zebrafish, but overexpression of Shh randomizes the situs of the heart and other visceral organs, most likely through the activity of the Nodal-related gene Ndr2. BMPs are expressed asymmetrically in the heart field (in orange), and BMP misexpression only affects the heart, pointing toward a specific role for BMPs in the development of this organ in zebrafish. It remains to be seen whether some other TGF-β (or other molecule) plays the role of repressing Ndr2. In zebrafish and Xenopus, unlike in chick and mouse, asymmetry of Nodal expression around the node has not been detected ( 48, 75 and 70). Image published in: Capdevila J et al. (2000) Copyright © 2000. Image reproduced with permission of the Publisher, Elsevier B. V. Larger Image Printer Friendly View

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