“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section spotlights significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms.
Leading the transformation (Dynamic Lkb1-TORC1 Signaling as a Possible Mechanism for Regulating the Endoderm-Intestine Transition by Kathryn E. Marshall, Amber J. Tomasini, Khadijah Makky, Suresh N. Kumar, and Alan N. Mayer, Dev Dyn239:3000–3012) During the endoderm–intestine transition (EIT) in zebrafish, the primitive gut tube shape-shifts into the mature intestine, a single-layered absorptive epithelium. Although many aspects of this transformation, including tissue remodeling, proliferation, and differentiation, are conserved in mammals, little is known about the mechanisms that regulate this elaborate process. Mayer and colleagues follow up on their previous work showing that EIT is regulated by the rapamycin-sensitive TOR complex 1 (TORC1), a downstream component of the TOR pathway known for activating anabolic pathways required for cell growth and proliferation. Here, they show that an upstream inhibitor of TORC1, the tumor-suppressor kinase Lkb1, transiently redistributes to a predominantly nuclear subcellular localization during mid-EIT in both mouse and zebrafish embryonic intestinal epithelium. Nuclear-localized Lkb1 is known to lack kinase activity, correlating nicely with an observed concomitant transient activation of both mouse and zebrafish TORC1. Consistent with the idea that Lkb also regulates the timing of EIT, morpholino knockdown of the gene results in precocious cell proliferation, expression of intestinal differentiation markers, and morphological changes associated with differentiation. Moreover, epistasis experiments confirm that the TOR pathway functions downstream of Lkb during EIT. Together, the data point to a novel mechanism for controlling tissue maturation. Future efforts will concentrate on elucidating signals upstream of Lkb1.
Who's right? What's left? (Far From Solved: A Perspective on What We Know About Early Mechanisms of Left–Right Asymmetry by Laura N. Vandenberg and Michael Levin, Dev Dyn239:3131–3146) What would be the state of modern science if researchers failed to challenge assumptions? In this spirit, Vandenberg and Levin dispute the nearly foregone conclusion that left–right (L–R) asymmetry—the laterality of gene expression, organ positioning, and morphology—originates from directional ciliary flow during gastrulation. In doing so, they remind readers of two alternative hypotheses for biased gene distribution: the differential strand segregation model, and the intracellular/physiology model whereby ion channels and other mechanisms create bioelectrical asymmetries. Fueling the debate, they cite experimental results that are inconsistent with the ciliary model. For example, many organisms generate conserved L–R asymmetries entirely without, or before, the development of cilia, and vertebrate mutants exist in which ciliary defects are dissociated from errors of laterality. The review concludes with a discussion of specific areas of investigation that should fill existing knowledge gaps, and level the playing field. No matter what side of the debate the reader is on, the authors convincingly drive home the argument that to ignore these alternative avenues of research would be misguided.
ASSET for C. elegans embryologists (ASSET: A Robust Algorithm for the Automated Segmentation and Standardization of Early Caenorhabditis elegans Embryos by Simon Blanchoud, Yemima Budirahardja, Félix Naef, and Pierre Gönczy, Dev Dyn239:3285–3296) The first cell cycle in the nematode Caenorhabditis elegans embryo is a sight to behold (see Supp. Movie S1, which is available online). In a stereotyped, yet seemingly chaotic manner, the two pronuclei lurch toward one another, and then move together to the cell center, while the surrounding cortex contracts, expands, and furrows. Not surprisingly, it can be difficult to ascertain whether a mutant's jiggle differs from a wild-type's wiggle. C. elegans embryologists need not fret any longer. Here, Gönczy and colleagues present an image analysis platform, Algorithm for the Segmentation and the Standardization of C. Elegans Time-lapse recordings (ASSET). ASSET automatically tracks behavior of subcellular structures in live embryos over time, and plots the data onto a standardized embryo, allowing for direct comparisons between specimens. As proof of principle, they monitor behavior of fluorescently labeled centrosomes, and reveal new findings about wild-type centrosomal movements and positioning. They also discover previously unreported differences among cortical contractions between wild-type embryos, and embryos depleted of SAPS-1, a protein phosphatase-6–associated protein. ASSET, incorporated into user-friendly Matlab software, takes the guesswork and tediousness out of analyzing basic cellular mechanisms. Let the quantitation of odd movements begin!