Shaping the zebrafish notochord

Cellular reorganization based on active cell motility and adhesion is the major means of morphogenesis in animal embryos, and is particularly elaborated in vertebrates. Nowhere is this fact more clearly shown than in the dorsal mesoderm of gastrulating zebrafish embryos. Here, occurring in the company of both cellular internalization at the blastoderm margin (Carmany-Rampey and Schier, 2001) (R. J. A., D. Faruque and M. L. Concha, unpublished) to form the mesoderm and an equally prominent spreading of the blastoderm by epiboly (Warga and Kimmel, 1990), there is a rapid and massive cellular reorganization. The reorganization underlies mesodermal convergence, meaning the narrowing of the tissue with respect to the embryonic axis (the anteroposterior, or AP axis), and mesodermal extension – the lengthening of the tissue with respect this axis. Our current view of the cellular behaviors that drive these tissue-level shape changes comes primarily from a series of studies of explanted Xenopus dorsal mesoderm (Shih and Keller, 1992a; Shih and Keller, 1992b; Keller et al., 2000). Molecular and genetic studies (including studies in zebrafish and other species) have enriched our current understanding (Solnica-Krezel, 1999; Tada and Concha, 2001; Wallingford and Harland, 2001; Myers et al., 2002a; Myers et al., 2002b). The explant studies in Xenopus show that dorsal mesodermal converges and extends largely by cell rearrangement within the tissue, and without dependence upon an external substrate (Shih and Keller, 1992a). Furthermore, from this work has evolved the concept of a single but complex cellular behavior, termed mediolateral intercalation behavior (MIB), which underlies the rearrangements (Fig. 1). The MIB hypothesis is elegant because a single force-generating cellular machine, distributed across a field of cells, produces both convergence and extension, both narrowing and elongation of the field. By the MIB hypothesis, as applied particularly to the domain of notochord-forming cells within dorsal mesoderm, motile and adhesive cells become polarized along one particular axis, the mediolateral (ML) axis. The polarity may depend on, and be coordinated within the field, by a noncanonical Wnt signaling planar polarity pathway (Choi and Han, 2002; Heisenberg et al., 2000). The cells take on a bipolar shape, elongating along the ML axis. This process requires that the individual cells all correctly orient actin-based cytoskeletal machinery that mediates motility, and perhaps also orient associated adhesion complexes on their plasma membranes (Montell, 1999; Zalik et al., 1999). Localized release of intracellular Ca2+, via connexin 43 channels (Essner et al., 1996), and activation of Rho GTPases may be crucial in such polarized cellular morphogenesis (Choi and Han, 2002; Hall and Nobes, 2000; Smith et al., 2000). The cells intercalate mediolaterally. To accomplish this, they all protrude filopodial processes both 873 Development 130, 873-887 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00314