Apical cell expansion maintained by Dusky-like establishes a scaffold for corneal lens morphogenesis.

The corneal lens is entirely composed of chitin and other apical extracellular matrix components, and it is not known how it acquires the biconvex shape that enables it to focus light onto the retina. We show here that the zona pellucida domain-containing protein Dusky-like is essential for normal corneal lens morphogenesis. Dusky-like transiently localizes to the expanded apical surfaces of the corneal lens-secreting cells and prevents them from undergoing apical constriction and apicobasal contraction.

Synergistic activation by Glass and Pointed promotes neuronal identity in the Drosophila eye disc.

The integration of extrinsic signaling with cell-intrinsic transcription factors can direct progenitor cells to differentiate into distinct cell fates. In the developing Drosophila eye, differentiation of photoreceptors R1-R7 requires EGFR signaling mediated by the transcription factor Pointed, and our single-cell RNA-Seq analysis shows that the same photoreceptors require the eye-specific transcription factor Glass. We find that ectopic expression of Glass and activation of EGFR signaling synergistically induce neuronal gene expression in the wing disc in a Pointed-dependent manner.

Two distinct mechanisms of Plexin A function in Drosophila optic lobe lamination and morphogenesis.

Visual circuit development is characterized by subdivision of neuropils into layers that house distinct sets of synaptic connections. We find that, in the Drosophila medulla, this layered organization depends on the axon guidance regulator Plexin A. In Plexin A null mutants, synaptic layers of the medulla neuropil and arborizations of individual neurons are wider and less distinct than in controls.

Apical cell expansion maintained by Dusky-like establishes a scaffold for corneal lens morphogenesis.

The biconvex shape of the corneal lens, which enables it to focus light onto the retina, arises by organized assembly of chitin and other apical extracellular matrix components. We show here that the Zona Pellucida domain-containing protein Dusky-like is essential for normal corneal lens morphogenesis. Dusky-like transiently localizes to the expanded apical surfaces of the corneal lens-secreting cells, and in its absence, these cells undergo apical constriction and apicobasal contraction.

Two distinct mechanisms of Plexin A function in optic lobe lamination and morphogenesis.

Unlabelled: Visual circuit development is characterized by subdivision of neuropils into layers that house distinct sets of synaptic connections. We find that in the medulla, this layered organization depends on the axon guidance regulator Plexin A. In null mutants, synaptic layers of the medulla neuropil and arborizations of individual neurons are wider and less distinct than in controls.

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The Blimp-1 transcription factor acts in non-neuronal cells to regulate terminal differentiation of the Drosophila eye.

The formation of a functional organ such as the eye requires specification of the correct cell types and their terminal differentiation into cells with the appropriate morphologies and functions. Here, we show that the zinc-finger transcription factor Blimp-1 acts in secondary and tertiary pigment cells in the Drosophila retina to promote the formation of a bi-convex corneal lens with normal refractive power, and in cone cells to enable complete extension of the photoreceptor rhabdomeres. Blimp-1 expression depends on the hormone ecdysone, and loss of ecdysone signaling causes similar differentiation defects.

Sidekick dynamically rebalances contractile and protrusive forces to control tissue morphogenesis.

Contractile actomyosin and protrusive branched F-actin networks interact in a dynamic balance, repeatedly contracting and expanding apical cell contacts to organize the epithelium of the developing fly retina. Previously we showed that the immunoglobulin superfamily protein Sidekick (Sdk) contributes to contraction by recruiting the actin binding protein Polychaetoid (Pyd) to vertices. Here we show that as tension increases during contraction, Sdk progressively accumulates at vertices, where it toggles to recruit the WAVE regulatory complex (WRC) to promote actin branching and protrusion.

An exon junction complex-independent function of Barentsz in neuromuscular synapse growth.

The exon junction complex controls the translation, degradation, and localization of spliced mRNAs, and three of its core subunits also play a role in splicing. Here, we show that a fourth subunit, Barentsz, has distinct functions within and separate from the exon junction complex in Drosophila neuromuscular development. The distribution of mitochondria in larval muscles requires Barentsz as well as other exon junction complex subunits and is not rescued by a Barentsz transgene in which residues required for binding to the core subunit eIF4AIII are mutated.

R7 photoreceptor axon targeting depends on the relative levels of expression in R7 and its synaptic partners.

As neural circuits form, growing processes select the correct synaptic partners through interactions between cell surface proteins. The presence of such proteins on two neuronal processes may lead to either adhesion or repulsion; however, the consequences of mismatched expression have rarely been explored. Here, we show that the CUB-LDL protein Lost and found (Loaf) is required in the UV-sensitive R7 photoreceptor for normal axon targeting only when Loaf is also present in its synaptic partners.

Specific Isoforms of the Guanine-Nucleotide Exchange Factor dPix Couple Neuromuscular Synapse Growth to Muscle Growth.

Developmental growth requires coordination between the growth rates of individual tissues and organs. Here, we examine how Drosophila neuromuscular synapses grow to match the size of their target muscles. We show that changes in muscle growth driven by autonomous modulation of insulin receptor signaling produce corresponding changes in synapse size, with each muscle affecting only its presynaptic motor neuron branches.

Sidekick Is a Key Component of Tricellular Adherens Junctions that Acts to Resolve Cell Rearrangements.

Tricellular adherens junctions are points of high tension that are central to the rearrangement of epithelial cells. However, the molecular composition of these junctions is unknown, making it difficult to assess their role in morphogenesis. Here, we show that Sidekick, an immunoglobulin family cell adhesion protein, is highly enriched at tricellular adherens junctions in Drosophila.

Reduced SERCA Function Preferentially Affects Wnt Signaling by Retaining E-Cadherin in the Endoplasmic Reticulum.

Calcium homeostasis in the lumen of the endoplasmic reticulum is required for correct processing and trafficking of transmembrane proteins, and defects in protein trafficking can impinge on cell signaling pathways. We show here that mutations in the endoplasmic reticulum calcium pump SERCA disrupt Wingless signaling by sequestering Armadillo/β-catenin away from the signaling pool. Armadillo remains bound to E-cadherin, which is retained in the endoplasmic reticulum when calcium levels there are reduced.

The Epidermal Growth Factor Receptor does not act in the nucleus.

Mammalian members of the ErbB family, including the epidermal growth factor receptor (EGFR), can regulate transcription, DNA replication and repair through nuclear entry of either the full-length proteins or their cleaved cytoplasmic domains. In cancer cells, these nuclear functions contribute to tumor progression and drug resistance. Here, we examined whether the single EGFR can also localize to the nucleus.

Sidekick is required in developing photoreceptors to enable visual motion detection.

The assembly of functional neuronal circuits requires growth cones to extend in defined directions and recognize the correct synaptic partners. Homophilic adhesion between vertebrate Sidekick proteins promotes synapse formation between retinal neurons involved in visual motion detection. We show here that Sidekick accumulates in specific synaptic layers of the developing motion detection circuit and is necessary for normal optomotor behavior.

The COP9 signalosome inhibits Cullin-RING E3 ubiquitin ligases independently of its deneddylase activity.

The COP9 signalosome inhibits the activity of Cullin-RING E3 ubiquitin ligases by removing Nedd8 modifications from their Cullin subunits. Neddylation renders these complexes catalytically active, but deneddylation is also necessary for them to exchange adaptor subunits and avoid auto-ubiquitination. Although deneddylation is thought to be the primary function of the COP9 signalosome, additional activities have been ascribed to some of its subunits.

Glass promotes the differentiation of neuronal and non-neuronal cell types in the Drosophila eye.

Transcriptional regulators can specify different cell types from a pool of equivalent progenitors by activating distinct developmental programs. The Glass transcription factor is expressed in all progenitors in the developing Drosophila eye, and is maintained in both neuronal and non-neuronal cell types. Glass is required for neuronal progenitors to differentiate as photoreceptors, but its role in non-neuronal cone and pigment cells is unknown.

COP9 signalosome subunits protect Capicua from MAPK-dependent and -independent mechanisms of degradation.

The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here, we show that mutations in the () gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes.

Drosophila Vps4 promotes Epidermal growth factor receptor signaling independently of its role in receptor degradation.

Endocytic trafficking of signaling receptors is an important mechanism for limiting signal duration. Components of the Endosomal Sorting Complexes Required for Transport (ESCRT), which target ubiquitylated receptors to intra-lumenal vesicles (ILVs) of multivesicular bodies, are thought to terminate signaling by the epidermal growth factor receptor (EGFR) and direct it for lysosomal degradation. In a genetic screen for mutations that affect Drosophila eye development, we identified an allele of Vacuolar protein sorting 4 (Vps4), which encodes an AAA ATPase that interacts with the ESCRT-III complex to drive the final step of ILV formation.

The exon junction complex controls transposable element activity by ensuring faithful splicing of the piwi transcript.

The exon junction complex (EJC) is a highly conserved ribonucleoprotein complex that binds RNAs during splicing and remains associated with them following export to the cytoplasm. While the role of this complex in mRNA localization, translation, and degradation has been well characterized, its mechanism of action in splicing a subset of Drosophila and human transcripts remains to be elucidated. Here, we describe a novel function for the EJC and its splicing subunit, RnpS1, in preventing transposon accumulation in both Drosophila germline and surrounding somatic follicle cells.

The metazoan-specific mediator subunit 26 (Med26) is essential for viability and is found at both active genes and pericentric heterochromatin in Drosophila melanogaster.

Human MED26 was originally purified in the cofactor required for the Sp1 activation complex (CRSP) as a 70-kDa component named CRSP70. This polypeptide was specific to metazoans and the “small” form of the Mediator complex. We report here that a Drosophila melanogaster homologue of MED26 similarly interacts with other components of the core Drosophila Mediator complex but not with the kinase module and is recruited to genes upon activation.

Retinal differentiation in Drosophila.

Drosophila eye development has been extensively studied, due to the ease of genetic screens for mutations disrupting this process. The eye imaginal disc is specified during embryonic and larval development by the Pax6 homolog Eyeless and a network of downstream transcription factors. Expression of these factors is regulated by signaling molecules and also indirectly by growth of the eye disc.

Trafficking of the EGFR ligand Spitz regulates its signaling activity in polarized tissues.

Epidermal growth factor receptor (EGFR) ligands undergo a complex series of processing events during their maturation to active signaling proteins. Like its mammalian homologs, the predominant Drosophila EGFR ligand Spitz is produced as a transmembrane pro-protein. In the secretory pathway, Spitz is cleaved within its transmembrane domain to release the extracellular signaling domain.

A screen for X-linked mutations affecting Drosophila photoreceptor differentiation identifies Casein kinase 1α as an essential negative regulator of wingless signaling.

The Wnt and Hedgehog signaling pathways are essential for normal development and are misregulated in cancer. The casein kinase family of serine/threonine kinases regulates both pathways at multiple levels. However, it has been difficult to determine whether individual members of this family have distinct functions in vivo, due to their overlapping substrate specificities.

Requirements for mediator complex subunits distinguish three classes of notch target genes at the Drosophila wing margin.

Spatial and temporal gene regulation relies on a combinatorial code of sequence-specific transcription factors that must be integrated by the general transcriptional machinery. A key link between the two is the mediator complex, which consists of a core complex that reversibly associates with the accessory kinase module. We show here that genes activated by Notch signaling at the dorsal-ventral boundary of the Drosophila wing disc fall into three classes that are affected differently by the loss of kinase module subunits.