runt

DEVELOPMENTAL BIOLOGY

Embryonic

See the embryonic expression pattern of run at the Berkeley Drosophila Genome Project Patterns of Gene Expression Site.

Double-staining immunolocalization experiments were used to determine the overlap of the Runt protein pattern with the patterns of Hairy, Even-skipped, and Fushi tarazu. The patterns of Runt and Hairy are complementary. Their phasing is shifted anteriorly by two cell diameters with respect to the complementary EVE and FTZ patterns (Kania, 1990).

In early germ band extended embryos, the pattern of runt expression changes from a pair-rule pattern to a segmental pattern, consisting of a 13-striped pattern. runt is also expressed in a dorsal patch of cells in the head. Antibodies against the Runt protein reveal that it is expressed in a subset of neuroblasts, ganglion-mother cells and neurons. A subset of these neurons also co-express the segmentation gene even-skipped. Neurons require runt activity independent of its activity during segmentation. Upon completion of germ band retraction, about 50 cells per hemisegment are stained in the CNS (Kanai, 1990). These results have been confirmed using a temperature-sensitive runt allele. The requirement for runt arises during an early stage of neurogenesis (Duffy, 1991).

See Chris Doe's Hyper-Neuroblast map site for information on the expression of runt in specific neuroblasts.

To identify X chromosomal genes required for salivary gland development in the Drosophila embryo, embryos hemizygous for EMS-induced lethal mutations were screened to find mutations causing gross morphological defects in salivary gland development. The parental strain carried a lac Z transgene on the second chromosome, which was specifically expressed in the salivary glands so the mutations could be unambiguously identified. Embryos from 3,383 lines were tested for salivary gland abnormalities following lacZ staining. From 63 lines exhibiting aberrant salivary gland phenotypes, 52 stable lines were established containing mutations affecting salivary gland development. From these, 39 lines could be assigned to nine complementation groups: armadillo, brinker, folded gastrulation, giant, hindsight, Notch, runt, stardust and twisted gastrulation (Lammel, 2000).

Mutations in loci involved in segmentation are expected to affect salivary gland development if they are required for PS 2 formation. runt is required for the refinement of the fushi tarazu (ftz) pattern. In the absence of ftz, Scr expression in most of the anterior cells of PS 2 is missing. Although it may seem attractive to propose that run acts via ftz, a more direct run function also seems plausible (Lammel, 2000 and references therein).

Asymmetric mRNA localization targets proteins to their cytoplasmic site of function. The mechanism of apical localization of wingless and pair-rule transcripts in the Drosophila blastoderm embryo has been elucidated by directly visualizing intermediates along the entire path of transcript movement. After release from their site of transcription, mRNAs diffuse within the nucleus and are exported to all parts of the cytoplasm, regardless of their cytoplasmic destinations. Endogenous and injected apical RNAs assemble selectively into cytoplasmic particles that are transported apically along microtubules. Cytoplasmic dynein is required for correct localization of endogenous transcripts and apical movement of injected RNA particles. It is proposed that dynein-dependent movement of RNA particles is a widely deployed mechanism for mRNA localization (Wilkie, 2001).

To study the mechanism of apical localization, whether actin and/or MTs are necessary for localization of injected mRNA was tested by preinjecting cytoskeletal inhibitors 10 min before injecting the RNA. It was found that preinjection of Cytochalasin B, at concentrations that disrupt the organization of actin filaments, has no affect on Runt mRNA localization. However, a similar disruption of nuclear position has been observed in the cortical cytoplasm. In contrast, preinjection of colcemid, which destabilizes blastoderm MTs, disrupts runt, wingless, and fushi tarazu RNA localization almost entirely. It is concluded that an intact MT cytoskeleton is required for apical localization of injected RNA and that actin does not play a major role in the process. However, some minor role for actin in apical localization of RNA cannot be excluded (Wilkie, 2001).

Whether the localization of injected RNA occurs by minus end directed MT-dependent motor movement was tested by preinjecting embryos with antibodies against Drosophila cytoplasmic dynein heavy chain (dhc). Two independently raised monoclonal antibodies against dhc are each sufficient to inhibit RUN, FTZ, and WG mRNA apical localization in most, or all, embryos. Either one, the anti-dynein antibody or the colcemid injections, is sufficient to cause apical RNA to partly diffuse away from the site of injection in a similar manner to embryos injected with HB RNA alone. Injected apical RNA does not diffuse in the absence of anti-dynein antibodies or Colcemid preinjections. These results suggest that apical RNA is tethered to MTs by dynein and that dynein is required for the transport of RNA particles (Wilkie, 2001).

To further test the involvement of cytoplasmic dynein in apical transcript localization, RNA was injected into mutant cytoplasmic dynein heavy chain (Dhc64C) embryos. A marked reduction was found in the speed of movement of injected apical targeted RNAs in dynein mutants. Cytoplasmic dynein is essential for many cellular processes, so strong mutations in Dhc64C are homozygous lethal in Drosophila and cannot be studied at the blastoderm stage. Instead hypomorphic allelic combinations of Dhc64C, which are viable in trans due to intragenic complementation, were used. In two different allelic combinations of Dhc64C, injected RNA particles move at speeds 60% to 70% slower than they do in wild-type. Staining Dhc64C mutant embryos with anti-tubulin antibodies showsthat MT distribution is indistinguishable from wild-type, indicating that the reduced speed of localization is not due indirectly to a disruption of the MTs. Instead, the reduction in speed is likely to show a direct requirement for dynein in particle transport (Wilkie, 2001).

Dynactin is a protein complex that is involved in coordinating the activities of cytoplasmic dynein, and is thought to be required for most forms of dynein-based transport. To test whether dynactin is also required for apical RNA localization, a large excess of p50/dynamitin is preinjected into embryos 10 min before injecting apically targeted RNA. p50/dynamitin causes a significant reduction in the speed of RNA particle movement. p50/dynamitin is a subunit of dynactin whose overexpression is a widely used method of disrupting the dynactin complex and demonstrating conclusively dynein-dependent motility. Dynactin is required for some cargo binding and for dynein processivity. It is concluded that apical transcript localization in the blastoderm embryo occurs by cytoplasmic dynein- and dynactin-mediated transport along MTs toward their minus ends (Wilkie, 2001).

It is thought that export and localization of apical mRNA in the blastoderm embryo can be divided into six distinct steps. (1) During or after completion of transcription and processing, transcripts are assembled into particles, which contain various hnRNPs and export factors, some of which may form part of the cytoplasmic localization machinery. (2) mRNA particles diffuse freely after release from the site of transcription and processing until they reach nuclear pore complexes (NPCs) on the nuclear periphery. (3) mRNA particles are exported through NPCs in all parts of the nuclear envelope. (4) The composition of the particles probably changes during export from the nucleus and in the cytoplasm to recruit dynein, dynactin, and associated proteins. (5) Particles attach to MTs and are actively transported to the apical cytoplasm. (6) Particle movement arrests in the apical cytoplasm, where they may associate with other particles and become anchored (Wilkie, 2001).

The Drosophila brain develops from the procephalic neurogenic region of the ectoderm. About 100 neural precursor cells (neuroblasts) delaminate from this region on either side in a reproducible spatiotemporal pattern. Neuroblast maps have been prepared from different stages of the early embryo (stages 9, 10 and 11, when the entire population of neuroblasts has formed), in which about 40 molecular markers representing the expression patterns of 34 different genes are linked to individual neuroblasts. In particular, a detailed description is presented of the spatiotemporal patterns of expression in the procephalic neuroectoderm and in the neuroblast layer of the gap genes empty spiracles, hunchback, huckebein, sloppy paired 1 and tailless; the homeotic gene labial; the early eye genes dachshund, eyeless and twin of eyeless; and several other marker genes (including castor, pdm1, fasciclin 2, klumpfuss, ladybird, runt and unplugged). Based on the combination of genes expressed, each brain neuroblast acquires a unique identity, and it is possible to follow the fate of individual neuroblasts through early neurogenesis. Furthermore, despite the highly derived patterns of expression in the procephalic segments, the co-expression of specific molecular markers discloses the existence of serially homologous neuroblasts in neuromeres of the ventral nerve cord and the brain. Taking into consideration that all brain neuroblasts are now assigned to particular neuromeres and individually identified by their unique gene expression, and that the genes found to be expressed are likely candidates for controlling the development of the respective neuroblasts, these data provide a basic framework for studying the mechanisms leading to pattern and cell diversity in the Drosophila brain, and for addressing those mechanisms that make the brain different from the truncal CNS (Urbach, 2003).

In the trunk, the pair-rule gene runt is expressed in segmental domains of the ventral neuroectoderm and in five NBs of row 2 and 3 and two NBs of row 5. Runt has also been shown to be expressed in an anterodorsal region of the blastoderm, corresponding to the presumptive head region. En/Runt antibody co-labelling reveals that this Runt domain contributes to the ocular segment. In addition to the ocular segment, patches of runt expression are in the intercalary, antennal and clypeolabral ectoderm, and in subsets of protocerebral and deutocerebral NBs. At stage 11, the protein is expressed in a total of 23 brain NBs, some of which initiate Runt expression after delamination from Runt-negative ectoderm, and in a large number of postmitotic cells until the end of embryogenesis (Urbach, 2003).

Effects of Mutation

Slam servers as a molecular marker for polarized cell behavior revealing functions of Eve, Runt, Myosin II and Bazooka in germband extension

During convergent extension in Drosophila, polarized cell movements cause the germband to narrow along the dorsal-ventral (D-V) axis and more than double in length along the anterior-posterior (A-P) axis. This tissue remodeling requires the correct patterning of gene expression along the A-P axis, perpendicular to the direction of cell movement. A-P patterning information results in the polarized localization of cortical proteins in intercalating cells. In particular, cell fate differences conferred by striped expression of the even-skipped and runt pair-rule genes are both necessary and sufficient to orient planar polarity. This polarity consists of an enrichment of nonmuscle myosin II at A-P cell borders and Bazooka/PAR-3 protein at the reciprocal D-V cell borders. Moreover, bazooka mutants are defective for germband extension. These results indicate that spatial patterns of gene expression coordinate planar polarity across a multicellular population through the localized distribution of proteins required for cell movement (Zallen, 2004).

Polarized cell movement during convergent extension ultimately derives from the asymmetric localization of proteins that direct cell motility. Interestingly, intercalating cells in the Drosophila germband display a polarized localization of the ectopically expressed Slam protein (Lecuit, 2002). Slam is present in a bipolar distribution that correlates spatially and temporally with intercalary behavior. These observations indicate that Slam can serve as a molecular marker for polarized cell behavior. Pair-rule patterning genes expressed in stripes along the A-P axis are necessary for Slam localization and, conversely, altering the geometry of their expression is sufficient to reorient Slam polarity. An endogenous planar polarity in intercalating cells has been shown to be manifested by the accumulation of nonmuscle myosin II at A-P cell borders and Bazooka/PAR-3 at D-V cell borders. Moreover, germband extension is defective in bazooka mutant embryos, supporting a model where molecular polarization of the cell surface is a prerequisite for polarized cell movement. Therefore, differences in gene expression along the A-P axis may direct planar polarity in intercalating cells through the creation of molecularly distinct cell-cell interfaces that differ in migratory potential (Zallen, 2004).

Cell movement during germband extension is oriented along the D-V axis, suggesting a mechanism that restricts the productive generation of motility to dorsal and ventral cell surfaces. Molecules that are asymmetrically localized during convergent extension may therefore contribute to the spatial regulation of cell motility. Interestingly, intercalating cells in the Drosophila germband display a polarized localization of the ectopically expressed Slam protein, a novel cytoplasmic factor required for cellularization in the early embryo (Lecuit, 2002). While proteins such as Armadillo/β-catenin are uniformly distributed at the cell surface, ectopic Slam is enriched in borders between neighboring cells along the A-P axis. This polarized Slam population is present in a punctate apical distribution, coincident with the adherens junction component Armadillo/β-catenin. Therefore, intercalating cells have distinct apical junctional domains that differ in their capacity for Slam association (Zallen, 2004).

Interestingly, the polarized distribution of ectopic Slam protein is spatially and temporally correlated with intercalary behavior. Slam polarity is not observed in Stage 6 embryos prior to the onset of intercalation. Slam accumulation at A-P cell borders first appears in late Stage 7, when cells of the germband initiate intercalation, and reaches its full extent during the period of sustained intercalation in Stage 8. In contrast, Slam is uniformly distributed in cells of the head region and the dorsal ectoderm, tissues which do not undergo intercalary movements. These results indicate that the polarized distribution of ectopic Slam protein is specific to intercalating cells and that Slam can therefore serve as a molecular marker for the visualization of polarized cell behavior (Zallen, 2004).

The enrichment of Slam at borders between neighboring cells along the A-P axis is consistent with two modes of localization: Slam could mark one side of each cell in a unipolar distribution, or Slam could localize to both anterior and posterior surfaces in a bipolar pattern. To distinguish between these possibilities, mosaic embryos were generated where Slam-expressing cells were juxtaposed with unlabeled cells, using the Horka mutation to induce sporadic chromosome loss in early embryos. Slam protein accumulates at anterior and posterior boundaries of mosaic clone, indicating that ectopic Slam protein is targeted to both anterior and posterior surfaces of intercalating cells in a symmetric, bipolar distribution. The bipolar localization of ectopic Slam corresponds well with the bidirectionality of cell movement during germband extension, where cells are equally likely to migrate dorsally or ventrally during intercalation. Bipolar motility is also observed during convergent extension in the presumptive Xenopus and Ciona notochords and in Xenopus neural plate cells in the absence of midline structures (Zallen, 2004).

To extend the spatial and temporal correlation between Slam polarity and cell movement, it was asked if this polarized Slam localization is achieved in mutants that are defective for intercalation. Cell intercalation is dependent on the transcriptional cascade that generates cell fates along the A-P axis, in the direction of tissue elongation and perpendicular to the migrations of individual cells. A-P patterning reflects the hierarchical action of maternal, gap, and pair-rule genes. Cell fate differences along the A-P axis are abolished in embryos maternally deficient for the bicoid, nanos, and torso-like genes (referred to as bicoid nanos torso-like mutants), and these mutant embryos do not exhibit intercalary behavior. Ectopic Slam is correctly targeted to the apical cell surface in bicoid nanos torso-like mutants, but fails to adopt a polarized distribution in the plane of the epithelium (Zallen, 2004).

Downstream of the maternal patterning genes, gap genes establish overlapping subdomains along the A-P axis. A quadruple mutant for the gap genes knirps, hunchback, forkhead, and tailless lacks A-P pattern within the germband while retaining terminal structures. This quadruple mutant exhibits severely reduced cell intercalation, and mutant embryos also display a loss of Slam polarity. The absence of planar polarity in A-P patterning mutants correlates with a more hexagonal appearance of germband cells, in contrast to the irregular morphology of wild-type intercalating cells (Zallen, 2004).

In response to maternal and gap genes, pair-rule patterning genes expressed in narrow stripes act in combination to assign each cell a distinct fate along the A-P axis. In particular, the even-skipped (eve) and runt pair-rule genes are essential for germband extension. This strong requirement for eve and runt during germband extension contrasts with the more subtle effects in mutants for other pair-rule genes such as hairy and ftz. Consistent with these defects in intercalation, eve and runt mutants also display aberrant Slam localization. These results establish a correlation between intercalary behavior and the polarized localization of the ectopic Slam marker (Zallen, 2004).

While eve and runt mutants fail to complete germband extension, they extend further than embryos lacking maternal and gap genes, suggesting that some intercalary behavior is retained. Consistent with this possibility, Slam polarity is only partially disrupted in eve and runt mutants. While some cells display an aberrant uniform Slam distribution, in other cells Slam is correctly enriched at A-P cell interfaces. Therefore, the residual intercalation in eve and runt mutants correlates with the establishment of planar polarity in a subset of germband cells (Zallen, 2004).

The disruption of Slam polarity in A-P patterning mutants demonstrates that proper gene expression along the A-P axis is required for planar polarity in intercalating cells. In particular, the Eve and Runt transcription factors are expressed in 7 stripes at the onset of germband extension and 14 stripes as intercalation proceeds. Each cell in the germband is assigned a fate distinct from its anterior and posterior neighbors through the graded and partially overlapping expression of these and other pair-rule genes. Slam preferentially accumulates at contacts between cells with different levels of pair-rule gene activity, suggesting a model where cells concentrate specific proteins at interfaces with neighbors that differ in A-P identity. To directly address this model, mosaic embryos were generated with altered patterns of pair-rule gene expression in order to artificially introduce differences between dorsal and ventral neighbors. It was then asked if Slam protein is aberrantly recruited to these ectopic juxtapositions between different cell types, even at interfaces that are perpendicular to the normal axis of polarity (Zallen, 2004).

The Horka mutation was used to generate embryos that ectopically express Eve or Runt in a mosaic pattern. When these genes are ubiquitously expressed, planar polarity is generally disrupted and Slam displays a more uniform localization. This disruption of Slam polarity correlates with defective germband extension in Eve and Runt overexpressing embryos. The effects of Eve and Runt overexpression are not mimicked by overexpression of other pair-rule proteins such as Paired, Odd-paired, or Sloppy-paired. Moreover, localized sources of Eve or Runt expression direct aberrant patterns of polarity in mosaic embryos. For example, mosaic embryos display circles of Slam polarity that are bordered by ectopic Eve clones. Similarly, Slam polarity in germband cells is diverted from its normal orientation to follow boundaries of Runt misexpression. These results demonstrate that ectopic sites of Eve and Runt expression can reorient Slam polarity at clone boundaries, even when these interfaces are perpendicular to the normal axis of polarity (Zallen, 2004).

In contrast to the reorientation of planar polarity at boundaries of Eve and Runt misexpression, cells distant from the clone often exhibited complex patterns of Slam localization. These patterns may arise from nonautonomous effects of pair-rule gene activity, as well as aberrant cell movements and ectopic folds that form at clone boundaries, suggestive of a disruption in cell adhesion. Therefore mosaic embryos were examined at Stage 7, prior to the onset of cell movement and ectopic fold formation. While early Stage 7 embryos do not normally exhibit Slam polarity, ectopic Eve induces a precocious accumulation of Slam at clone boundaries. In contrast, ectopic Runt only occasionally induces a subtle polarity at Stage 7. The more potent effect of the eve transgene may reflect higher levels of ectopic expression compared to the endogenous eve stripes. These mosaic experiments indicate that differences in gene expression play an instructive role in the generation of planar polarity in intercalating cells. While Eve and Runt are both sufficient for planar polarity, the absence of either gene alone disrupts polarity. However, the defects in eve or runt single mutants may result from a combined disruption of multiple pair-rule genes; loss of eve leads to altered runt expression and vice versa (Zallen, 2004).

Generation of planar polarity by ectopic Eve expression is subject to the same spatial requirements as in wild-type polarity: Eve clones in the head region failed to induce polarity, suggesting that these cells are resistant to Eve-dependent polarization. In contrast, ectopic Runt expression in the head led to a concentration of Slam at clone boundaries, despite the fact that these cells do not normally display Slam polarity or intercalary behavior. These results indicate that in contrast to Eve, Runt can induce planar polarity in head cells, raising the possibility of functional distinctions between Eve and Runt target genes (Zallen, 2004).

The Eve and Runt transcription factors ultimately direct Slam polarity and cell intercalation through the transcriptional regulation of target genes. To identify downstream effectors involved in this process, components of the noncanonical planar cell polarity (PCP) pathway, which is required for convergent extension in vertebrates, were examined. Germband extension occurs normally in the majority of embryos lacking the Frizzled and Frizzled2 receptors. Similarly, germband extension is unaffected in the absence of Dishevelled. Moreover, dishevelled mutants exhibit a normal polarization of the Slam marker. These results demonstrate that molecular and behavioral properties of planar polarity in the Drosophila germband do not require Frizzled or Dishevelled function (Zallen, 2004).

The polarized distribution of ectopic Slam in intercalating cells provides the first clue to a molecular distinction between D-V cell interfaces that generate productive cell motility and A-P interfaces that do not. However, endogenous Slam mRNA and protein are not detected during germband extension, indicating that Slam may not play a functional role in cell intercalation. Slam colocalizes with the Zipper nonmuscle myosin II heavy chain subunit during cellularization and when Slam is ectopically expressed at germband extension (Lecuit, 2002). Therefore, the endogenous distribution of myosin II was examined during germband extension in wild-type embryos. During cell intercalation, myosin II is present in a punctate distribution at the apical cell surface, colocalizing with the adherens junction component Armadillo/β-catenin. In Stage 8 embryos, apical myosin II protein accumulates at interfaces between cells along the A-P axis. Slam can enhance this polarized localization when ectopically expressed (Lecuit, 2002), suggesting that Slam and myosin II may associate with a common localization machinery. Myosin II polarity is not apparent in Stage 6 or early Stage 7 embryos that have not begun intercalation, indicating that the enrichment of myosin II at A-P interfaces is specific to intercalating cells (Zallen, 2004).

The localized distribution of myosin II is not as pronounced as that of ectopic Slam, suggesting that additional asymmetries contribute to the polarization of intercalating cells. To identify such proteins, the localization was examined of components implicated in cell polarity in other cell types. In particular, the PDZ domain protein Bazooka/PAR-3 participates in both apical-basal and planar polarity. Bazooka/PAR-3 also exhibits a polarized distribution in intercalating cells. Bazooka, like myosin II, is present in a punctate apical distribution, coincident with the adherens junction component Armadillo/β-catenin. However, in contrast to the accumulation of myosin II at A-P cell interfaces, Bazooka is enriched in the reciprocal D-V interfaces. Bazooka polarity is specific to intercalating cells, where it first appears at the onset of intercalary movements in late Stage 7. Bazooka polarity is not observed in cells of the head region, which do not undergo intercalation, nor is it observed in germband cells following the completion of germband extension at Stage 9 (Zallen, 2004).

To characterize the relationship between cell shape and the polarized localization of cortical proteins, the orientation of cell borders was measured as an angle relative to the A-P axis (with A-P interfaces closer to 90° and D-V interfaces closer to 0° and 180°). Interfaces from embryos stained for Bazooka and myosin II were ranked according to mean fluorescence intensity as a relative measure of protein distribution. These results illustrate that Bazooka and myosin II are enriched in distinct sets of cell-cell interfaces that adopt largely nonoverlapping orientations relative to the A-P axis. This quantitation confirms the visual impression from confocal images and demonstrates that the molecular composition of a cell surface domain is a reliable predictor of its orientation within the epithelial cell sheet (Zallen, 2004).

The polarized localization of Bazooka is abolished in the absence of A-P patterning information in bicoid nanos torso-like mutant embryos. A similar disruption of myosin II polarity is observed in A-P patterning mutants. The A-P patterning system may therefore mediate cell intercalation through the polarized accumulation of cell surface-associated proteins. Bazooka participates in a conserved protein complex containing the atypical PKC (DaPKC), and DaPKC is also enriched in D-V cell interfaces during germband extension (Zallen, 2004).

To determine whether the polarized Bazooka/PAR-3 protein is functionally required for germband extension, homozygous bazooka (baz) mutant embryos were examined. In zygotic baz mutants, residual Bazooka protein persists from maternal stores and is often, but not always, correctly distributed along the apical-basal and planar axes. Despite this maternal Bazooka contribution, loss of zygotic Bazooka disrupts germband extension. In wild-type embryos, the posterior end of the extended germband is located at 70% egg length from the posterior pole. Of the progeny of baz^YD97/+ females and wild-type males, 72% were wild-type-like, 25% were partially defective, and 3% were strongly defective. These results demonstrate that Bazooka is required for normal germband extension (Zallen, 2004).

Bazooka/PAR-3 and the associated DmPAR-6 and DaPKC components also influence epithelial cell polarity along the apical-basal axis. To address the possibility that germband extension defects may occur indirectly as a result of disrupted apical-basal polarity, properties of apical-basal polarity were examined in zygotic baz mutants, where some functions are carried out by maternal gene products. Zygotic baz mutant embryos exhibit several signs of normal apical-basal polarity at gastrulation, including a monolayer epithelial morphology in the germband and the correct distribution of proteins to apical and lateral membrane domains. This is consistent with findings that zygotic baz mutants exhibit proper localization of the Armadillo/β-catenin adherens junction component prior to Stage 10 of embryogenesis. These results demonstrate that properties of apical-basal polarity are established correctly in baz mutant embryos during germband extension, consistent with a direct role for Bazooka in cell movements along the planar axis, independent of its later effects on apical-basal polarity (Zallen, 2004).

The local reorientation of planar polarity in response to Eve and Runt expression argues that planar polarity is generated by cell-cell interactions, rather than a distant polarizing cue. In addition to these local effects of Eve and Runt on planar polarity, Slam polarity frequently adopted a circular pattern in mosaic embryos, even when Eve and Runt were not present along the entire circumference of the circle. This unexpected configuration indicates that polarizing information can propagate from cell to cell downstream of an Eve-dependent signal. A similar relay mechanism is suggested by the swirling patterns of wing hair polarity that persist in Drosophila mutants defective for the PCP signaling pathway. Therefore, mechanisms of cell-cell communication may reinforce local polarizing events in the organization of a two-dimensional cell population (Zallen, 2004).

Planar polarity in Drosophila germband extension is locally established through the concentration of specific proteins at sites of contact between cells with different levels of Eve and Runt expression. Cells can monitor the identity of their neighbors through qualitative or quantitative differences in the activity of cell surface proteins, perhaps through ligand-receptor mediated signaling events or adhesion-based cell sorting. Transcriptional targets of Eve and Runt are therefore likely to include components that mediate intercellular signaling events involved in the transmission of polarizing information during multicellular reorganization (Zallen, 2004).

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date revised: 10 April 2008











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