Preface Animal development requires a carefully orchestrated cascade of cell fate specification events and cellular movements. A surprisingly small number of choreographed cellular behaviours are used repeatedly to shape the animal body plan. Among these, cell intercalation lengthens or spreads a tissue at the expense of narrowing along an orthogonal axis. Key steps in the polarization of both mediolaterally and radially intercalating cells have now been clarified. In these different contexts, intercalation seems to require a distinct combination of mechanisms, including adhesive changes that allow cells to rearrange, cytoskeletal events through which cells exert the forces needed for cell neighbour exchange, and in some cases regulation of these processes through planar cell polarity.

Cell intercalation is a fundamental, coordinated cell rearrangement process that shapes tissues throughout animal development. Studies of intercalation within epithelia have focused almost exclusively on the localized constriction of specific apical junctions. Another widely deployed yet poorly understood alternative mechanism of epithelial intercalation relies on basolateral protrusive activity. Using the dorsal embryonic epidermis of C. elegans, we have investigated this alternative mechanism using high-resolution live cell microscopy and genetic analysis. We find that as dorsal epidermal cells migrate past one another, they produce F-actin rich protrusions polarized at their extending (medial) edges. These protrusions are controlled by the C. elegans Rac and RhoG orthologs, CED-10 and MIG-2, which function redundantly to polarize actin polymerization upstream of the WAVE complex and WASP, respectively. We also identify UNC-73, the C. elegans ortholog of Trio, as a guanine nucleotide exchange factor (GEF) upstream of both CED-10/Rac and MIG-2/RhoG. Further, we identify a novel polarizing cue, CRML-1, the ortholog of human Capping Arp2/3 Myosin I Linker (CARMIL), that localizes to the nonprotrusive lateral edges of dorsal cells. CRML-1 genetically suppresses UNC-73/Trio function, and indirectly, actin polymerization. This network identifies a novel, molecularly conserved cassette that regulates epithelial intercalation via basolateral protrusive activity.

Summary α-catenin is central to recruitment of actin networks to the cadherin-catenin complex (CCC) [1, 2], but how such networks are subsequently stabilized against applied stress during morphogenesis is poorly understood. To identify proteins that functionally interact with α-catenin in this process, we performed enhancer screening using a weak allele of the C. elegans α-catenin, hmp-1, and identified UNC-94/tropomodulin. Tropomodulins (Tmods) cap the minus ends of F-actin in sarcomeres [3]. They also regulate lamellipodia [4], can promote actin nucleation [5], and are required for normal cardiovascular development [6, 7] and neuronal growth cone morphology [8]. Tmods regulate the morphology of cultured epithelial cells [9], but their role in epithelia in vivo remains unexplored. We find that UNC-94 is enriched within a HMP-1-dependent junctional actin network at epidermal adherens junctions subject to stress during morphogenesis. Loss of UNC-94 leads to discontinuity of this network, and high-speed filming of hmp-1(fe4);unc-94(RNAi) embryos reveals large junctional displacements that depend on the Rho pathway. In vitro, UNC-94 acts in combination with HMP-1, leading to longer actin bundles than with HMP-1 alone. Our data suggest Tmods protect actin filaments recruited by α-catenin from minus-end subunit loss, enabling them to withstand the stresses of morphogenesis.

Students’ study habits during independent study sessions were examined. Controlling for preparation, total study time, and class absences, it was found that active study strategy use positively predicted exam score, study spacing potential did not predict exam score, and distraction during study sessions negatively predicted exam score.

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation.