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Some organs in animals display left-right (LR) asymmetry. To better understand LR asymmetric morphogenesis in Drosophila, we studied LR directional rotation of the hindgut epithelial tube. Hindgut epithelial cells adopt a LR asymmetric (chiral) cell shape within their plane, and we refer to this cell behavior as planar cell-shape chirality (PCC). Drosophila E-cadherin (DE-Cad) is distributed to cell boundaries with LR asymmetry, which is responsible for the PCC formation. Myosin ID switches the LR polarity found in PCC and in DE-Cad distribution, which coincides with the direction of rotation. An in silico simulation showed that PCC is sufficient to induce the directional rotation of this tissue. Thus, the intrinsic chirality of epithelial cells in vivo is an underlying mechanism for LR asymmetric tissue morphogenesis.

Morphogens, such as Decapentaplegic (Dpp) in the fly imaginal discs, form graded concentration profiles that control patterning and growth of developing organs. In the imaginal discs, proliferative growth is homogeneous in space, posing the conundrum of how morphogen concentration gradients could control position-independent growth. To understand the mechanism of proliferation control by the Dpp gradient, we quantified Dpp concentration and signaling levels during wing disc growth. Both Dpp concentration and signaling gradients scale with tissue size during development. On average, cells divide when Dpp signaling levels have increased by 50%. Our observations are consistent with a growth control mechanism based on temporal changes of cellular morphogen signaling levels. For a scaling gradient, this mechanism generates position-independent growth rates.

Vertebrate segmentation relies on a mechanism characterized by oscillating gene expression. Whether this mechanism is used by other segmented animals has been controversial. Rigorous proof of cyclic expression during arthropod segmentation has been lacking. We find that the segmentation gene odd-skipped (Tc-odd) oscillates with a two-segment periodicity in the beetle Tribolium castaneum. By bisecting embryos and culturing the two halves over different time intervals, we demonstrate that Tc-odd cycles with a period of about 95 minutes at 30°C. Using live imaging and cell tracking in green fluorescent protein-expressing embryos, we can exclude that cell movements explain this dynamic expression. Our results show that molecular oscillators represent a common feature of segmentation in divergent animals and help reconcile the contrasting paradigms of insect and vertebrate segmentation.

Understanding cell morphogenesis during metazoan development requires knowledge of how cells and the extracellular matrix produce and respond to forces. We investigated how apoptosis, which remodels tissue by eliminating supernumerary cells, also contributes forces to a tissue (the amnioserosa) that promotes cell-sheet fusion (dorsal closure) in the Drosophila embryo. We showed that expression in the amnioserosa of proteins that suppress or enhance apoptosis slows or speeds dorsal closure, respectively. These changes correlate with the forces produced by the amnioserosa and the rate of seam formation between the cell sheets (zipping), key processes that contribute to closure. This apoptotic force is used by the embryo to drive cell-sheet movements during development, a role not classically attributed to apoptosis.

Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila . Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia. The age of the stem cell: a cap on spermatogenesis Adult stem cell populations in blood, epithelia and sperm maintain highly differentiated short-lived cell populations through asymmetric division, generating a self-renewing stem cell and a differentiating cell at each division. Disrupting the balance between renewal and differentiation can lead to over-proliferation (and tumorigenesis) or stem-cell depletion (and tissue degeneration). Using the Drosophila male germ line as a model, Cheng et al . studied the effects of tissue ageing on asymmetric stem cell division. Normally, germ-cell centrosomes are precisely oriented within their niche and asymmetric stem cell division is assured. The experiments showed that changes in stem cell orientation with age can halt or delay cell division, and contribute to a decline in spermatogenesis. Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. This paper shows that changes in stem cell orientation within the niche during ageing contribute to the decline in spermatogenesis in Drosophila male germ line.

Planarian flatworms can regenerate heads at anterior-facing wounds and tails at posterior-facing wounds throughout the body. How this regeneration polarity is specified has been a classic problem for more than a century. We identified a planarian gene, Smed-βcatenin-1, that controls regeneration polarity. Posterior-facing blastemas regenerate a head instead of a tail in Smed-βcatenin-1(RNAi) animals. Smed-βcatenin-1 is required after wounding and at any posterior-facing wound for polarity. Additionally, intact Smed-βcatenin-1(RNAi) animals display anteriorization during tissue turnover. Five Wnt genes and a secreted Frizzled-related Wnt antagonist-like gene are expressed in domains along the anteroposterior axis that reset to new positions during regeneration, which suggests that Wnts control polarity through Smed-βcatenin-1. Our data suggest that β-catenin specifies the posterior character of the anteroposterior axis throughout the Bilateria and specifies regeneration polarity in planarians.

Shaping a developing organ or embryo relies on the spatial regulation of cell division and shape. However, morphogenesis also occurs through changes in cell-neighbourhood relationships produced by intercalation. Intercalation poses a special problem in epithelia because of the adherens junctions, which maintain the integrity of the tissue. Here we address the mechanism by which an ordered process of cell intercalation directs polarized epithelial morphogenesis during germ-band elongation, the developmental elongation of the Drosophila embryo. Intercalation progresses because junctions are spatially reorganized in the plane of the epithelium following an ordered pattern of disassembly and reassembly. The planar remodelling of junctions is not driven by external forces at the tissue boundaries but depends on local forces at cell boundaries. Myosin II is specifically enriched in disassembling junctions, and its planar polarized localization and activity are required for planar junction remodelling and cell intercalation. This simple cellular mechanism provides a general model for polarized morphogenesis in epithelial organs.

Stem cell niches are locations where stem cells reside and self-renew. Although studies have shown how niches maintain stem cell fate during tissue homeostasis, less is known about their roles in establishing stem cells. The adult Drosophila midgut is maintained by intestinal stem cells (ISCs); however, how they are established is unknown. Here, we show that an ISC progenitor generates a niche cell via Notch signaling. This niche uses the bone morphogenetic protein 2/4 homolog, decapentaplegic, to allow progenitors to divide in an undifferentiated state and subsequently breaks down and dies, resulting in the specification of ISCs in the adult midgut. Our results demonstrate a paradigm for stem cell-niche biology, where progenitors generate transient niches that determine stem cell fate and may give insights into stem cell specification in other tissues.

Genetic mosaic analysis in Drosophila melanogaster shows that there are two classes of cells in the budding tracheal branches: those that migrate to the tip, and those that follow these lead cells and form a tube. The position of the cell results from competition within the population, with those expressing the highest level of FGF taking the lead positions at the tip, and the others forming the branch stalk. Many organs are composed of tubular networks that arise by branching morphogenesis in which cells bud from an epithelium and organize into a tube 1 , 2 , 3 . Fibroblast growth factors (FGFs) and other signalling molecules have been shown to guide branch budding and outgrowth 4 , 5 , 6 , 7 , but it is not known how epithelial cells coordinate their movements and morphogenesis. Here we use genetic mosaic analysis in Drosophila melanogaster to show that there are two functionally distinct classes of cells in budding tracheal branches: cells at the tip that respond directly to Branchless FGF and lead branch outgrowth, and trailing cells that receive a secondary signal to follow the lead cells and form a tube. These roles are not pre-specified; rather, there is competition between cells such that those with the highest FGF receptor activity take the lead positions, whereas those with less FGF receptor activity assume subsidiary positions and form the branch stalk. Competition appears to involve Notch-mediated lateral inhibition that prevents extra cells from assuming the lead. There may also be cooperation between budding cells, because in a mosaic epithelium, cells that cannot respond to the chemoattractant, or respond only poorly, allow other cells in the epithelium to move ahead of them.

In nervous systems with bilateral symmetry, many neurons project axons across the midline to the opposite side. In each segment of the Drosophila embryonic nervous system, axons that display this projection pattern choose one of two distinct tracts: the anterior or posterior commissure. Commissure choice is controlled by Derailed, an atypical receptor tyrosine kinase expressed on axons projecting in the anterior commissure. Here we show that Derailed keeps these axons out of the posterior commissure by acting as a receptor for Wnt5, a member of the Wnt family of secreted signalling molecules. Our results reveal an unexpected role in axon guidance for a Wnt family member, and show that the Derailed receptor is an essential component of Wnt signalling in these guidance events.