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Summary There are six members of the tubulin superfamily in eukaryotes [1]. Alpha- and beta-tubulin form a heterodimer that polymerizes to form microtubules, and gamma-tubulin nucleates microtubules as a component of the gamma-tubulin ring complex. Alpha-, beta-, and gamma-tubulin are conserved in all eukaryotes. In contrast, delta- and epsilon-tubulin are conserved in many, but not all, eukaryotes and are associated with centrioles, although their molecular function is unclear [2–7]. Zeta-tubulin is the sixth and final member of the tubulin superfamily and is largely uncharacterized. We find that zeta-, epsilon-, and delta-tubulin form an evolutionarily co-conserved module, the ZED module, that has been lost at several junctions in eukaryotic evolution and that zeta- and delta-tubulin are evolutionarily interchangeable. Humans lack zeta-tubulin but have delta-tubulin. In Xenopus multiciliated cells, zeta-tubulin is a component of the basal foot, a centriolar appendage that connects centrioles to the apical cytoskeleton, and co-localizes there with epsilon-tubulin. Depletion of zeta-tubulin results in disorganization of centriole distribution and polarity in multiciliated cells. In contrast with multiciliated cells, zeta-tubulin in cycling cells does not localize to centrioles and is associated with the TRiC/CCT cytoplasmic chaperone complex. We conclude that zeta-tubulin facilitates interactions between the centrioles and the apical cytoskeleton as a component of the basal foot in differentiated cells and propose that the ZED tubulins are important for centriole functionalization and orientation of centrioles with respect to cellular polarity axes.

Cilia are microtubule based cellular projections that serve a wide variety of essential functions in animal cells. Defects in cilia structure or function have recently emerged as etiological mechanisms underpinning diverse human diseases. While many eukaryotic cells possess only one or two cilia, some cells, including those of many unicellular organisms, exhibit extensive multiciliation. In vertebrates, multiciliated cells (MCCs) are a specialized population of post-mitotic cells decorated with dozens of motile cilia that beat in a polarized and synchronized fashion to drive directed fluid flow across an epithelium. Dysfunction of human MCCs is associated with diseases of the brain, airway and reproductive tracts. Despite their importance, MCCs are relatively poorly studied and we are only beginning to understand the mechanisms underlying their development and function. Here, we briefly review the general phylogeny and physiology of multiciliation and detail our current understanding of the developmental and cellular events underlying the formation, maturation, and function of MCCs in vertebrates.

Background: The morphogenetic events of early vertebrate development generally involve the combined actions of several populations of cells, each engaged in a distinct behavior. Neural tube closure, for instance, involves apicobasal cell heightening, apical constriction at hingepoints, convergent extension of the midline, and pushing by the epidermis. Although a large number of genes are known to be required for neural tube closure, in only a very few cases has the affected cell behavior been identified. For example, neural tube closure requires the actin binding protein Shroom, but the cellular basis of Shroom function and how it influences neural tube closure remain to be elucidated. Results: We show here that expression of Shroom is sufficient to organize apical constriction in transcriptionally quiescent, naive epithelial cells but not in non-polarized cells. Shroom-induced apical constriction was associated with enrichment of apically localized actin filaments and required the small GTPase Rap1 but not Rho. Endogenous Xenopus shroom was found to be expressed in cells engaged in apical constriction. Consistent with a role for Shroom in organizing apical constriction, disrupting Shroom function resulted in a specific failure of hingepoint formation, defective neuroepithelial sheet-bending, and failure of neural tube closure. Conclusions: These data demonstrate that Shroom is an essential regulator of apical constriction during neurulation. The finding that a single protein can initiate this process in epithelial cells establishes that bending of epithelial sheets may be patterned during development by the regulation of expression of single genes.

The PCP signaling cascade controls polarized cell behaviors in various organisms. New evidence suggests that this signaling cascade also controls the deposition of extracellular matrix during vertebrate gastrulation.

BMPs are essential regulators of cell fate during early embryonic development. Molecular genetics and in vivo imaging of cell behaviors in zebrafish now demonstrate a role for BMPs in the control of cell adhesion. The work reveals an important new mechanism governing cell movements during gastrulation.