gone early, a novel germline factor, ensures the proper size of the stem cell precursor pool in the Drosophila ovary.

In order to sustain lifelong production of gametes, many animals have evolved a stem cell-based gametogenic program. In the Drosophila ovary, germline stem cells (GSCs) arise from a pool of primordial germ cells (PGCs) that remain undifferentiated even after gametogenesis has initiated. The decision of PGCs to differentiate or remain undifferentiated is regulated by somatic stromal cells: specifically, epidermal growth factor receptor (EGFR) signaling activated in the stromal cells determines the fraction of germ cells that remain undifferentiated by shaping a Decapentaplegic (Dpp) gradient that represses PGC differentiation.

Egfr signaling controls the size of the stem cell precursor pool in the Drosophila ovary.

In many animals, germline progenitors are kept undifferentiated to give rise to germline stem cells (GSCs), enabling continuous production of gametes throughout animal life. In the Drosophila ovary, GSCs arise from a subset of primordial germ cells (PGCs) that stay undifferentiated even after gametogenesis has started. How a certain population of PGCs is protected against differentiation, and the significance of its regulatory mechanisms on GSC establishment remain elusive.

Compartmentalization within neurites: its mechanisms and implications.

Neurons are morphologically characterized by long processes extending from a cell body. These processes, the dendrites and axon, are major sub-cellular compartments defined by morphological, molecular, and functional differences. However, evidence from vertebrates and invertebrates suggests that, based on molecular distribution, individual axons and dendrites are further divided into distinct compartments; many membrane molecules involved in axon guidance and synapse formation are localized to specific segments of axons or dendrites that share a boundary of localization.

Intra-axonal patterning: intrinsic compartmentalization of the axonal membrane in Drosophila neurons.

In the developing nervous system, distribution of membrane molecules, particularly axon guidance receptors, is often restricted to specific segments of axons. Such localization of membrane molecules can be important for the formation and function of neural networks; however, how this patterning within axons is achieved remains elusive. Here we show that Drosophila neurons in culture establish intra-axonal patterns in a cell-autonomous manner; several membrane molecules localize to either proximal or distal axon segments without cell-cell contacts.

Midline governs axon pathfinding by coordinating expression of two major guidance systems.

Formation of the neural network requires concerted action of multiple axon guidance systems. How neurons orchestrate expression of multiple guidance genes is poorly understood. Here, we show that Drosophila T-box protein Midline controls expression of genes encoding components of two major guidance systems: Frazzled, ROBO, and Slit.

TFIIH controls developmentally-regulated cell cycle progression as a holocomplex.

Basal transcription factor, TFIIH, is a multifunctional complex that carries out not only transcription but also DNA repair and cell cycle control. TFIIH is composed of two sub-complexes: core TFIIH and Cdk-activating kinase (CAK). In vitro studies suggest that CAK is sufficient for cell cycle regulation, whereas core TFIIH is required for DNA repair.

Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers.

Hippocampal mossy fibers project preferentially to the stratum lucidum, the proximal-most lamina of the suprapyramidal region of CA3. The molecular mechanisms that govern this lamina-restricted projection are still unknown. We examined the projection pattern of mossy fibers in mutant mice for semaphorin receptors plexin-A2 and plexin-A4, and their ligand, the transmembrane semaphorin Sema6A.

Local caspase activity directs engulfment of dendrites during pruning.

Pruning is important for sculpting neural circuits, as it removes excessive or inaccurate projections. Here we show that the removal of sensory neuron dendrites during pruning in Drosophila melanogaster is directed by local caspase activity. Suppressing caspase activity prevented dendrite removal, whereas a global activation of caspases within a neuron caused cell death.

DRONC coordinates cell death and compensatory proliferation.

Accidental cell death often leads to compensatory proliferation. In Drosophila imaginal discs, for example, gamma-irradiation induces extensive cell death, which is rapidly compensated by elevated proliferation. Excessive compensatory proliferation can be artificially induced by "undead cells" that are kept alive by inhibition of effector caspases in the presence of apoptotic stimuli.

ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized Netrin.

Networks in the CNS consist of neural modules that are connected in a repetitive array. Whereas individual modules contain guidance information along which axons track within the unit, these guidance cues hinder axon extension across module boundaries. We investigated how axons solve this 'boundary problem' by analyzing the longitudinal connections of neuromeres in Drosophila melanogaster.

Cell-type specific utilization of multiple negative feedback loops generates developmental constancy.

Signaling pathways generally contain multiple negative regulators that are induced by the signal they repress, constructing negative feedback loops. Although such negative regulators are often expressed in a tissue- or cell-type specific manner during development, little is known about the significance of their differential expression patterns and possible interactions. We show the role and interplay of two cell-type specific negative feedback loops during specification of photoreceptor neurons in the Drosophila compound eye, a process that occurs via epidermal growth factor (EGF)-mediated sequential induction through the activation of the Ras/MAPK signaling pathway.

seven-up Controls switching of transcription factors that specify temporal identities of Drosophila neuroblasts.

Drosophila neuronal stem cell neuroblasts (NB) constantly change character upon division, to produce a different type of progeny at the next division. Transcription factors Hunchback (HB), Krüppel (KR), Pdm (PDM), etc. are expressed sequentially in each NB and act as determinants of birth-order identity.

Coactivator MBF1 preserves the redox-dependent AP-1 activity during oxidative stress in Drosophila.

Basic leucine zipper proteins Jun and Fos form the dimeric transcription factor AP-1, essential for cell differentiation and immune and antioxidant defenses. AP-1 activity is controlled, in part, by the redox state of critical cysteine residues within the basic regions of Jun and Fos. Mutation of these cysteines contributes to oncogenic potential of Jun and Fos.

A conserved developmental program for sensory organ formation in Drosophila melanogaster.

Different sensory organs, such the eye and ear, are widely thought to have separate origins, guided by distinct organ-specific factors that direct all aspects of their development. Previous studies of the D. melanogaster gene eyeless (ey) and its vertebrate homolog Pax6 suggested that this gene acts in such a manner and specifically drives eye development.

EDL/MAE regulates EGF-mediated induction by antagonizing Ets transcription factor Pointed.

Inductive patterning mechanisms often use negative regulators to coordinate the effects and efficiency of induction. During Spitz EGF-mediated neuronal induction in the Drosophila compound eye and chordotonal organs, Spitz causes activation of Ras signaling in the induced cells, resulting in the activation of Ets transcription factor Pointed P2. We describe developmental roles of a novel negative regulator of Ras signaling, EDL/MAE, a protein with an Ets-specific Pointed domain but not an ETS DNA-binding domain.

Drosophila homeodomain protein REPO controls glial differentiation by cooperating with ETS and BTB transcription factors.

In Drosophila, cell-fate determination of all neuroectoderm-derived glial cells depends on the transcription factor Glial cells missing (GCM), which serves as a binary switch between the neuronal and glial cell fates. Because the expression of GCM is restricted to the early phase of glial development, other factors must be responsible for the terminal differentiation of glial cells. Expression of three transcription factors, Reversed Polarity (REPO), Tramtrack p69 (TTK69) and PointedP1 (PNTP1), is induced by GCM in glial cells.

Drosophila MBF1 is a co-activator for Tracheae Defective and contributes to the formation of tracheal and nervous systems.

During gene activation, the effect of binding of transcription factors to cis-acting DNA sequences is transmitted to RNA polymerase by means of co-activators. Although co-activators contribute to the efficiency of transcription, their developmental roles are poorly understood. We used Drosophila to conduct molecular and genetic dissection of an evolutionarily conserved but unique co-activator, Multiprotein Bridging Factor 1 (MBF1), in a multicellular organism.

Context-dependent utilization of Notch activity in Drosophila glial determination.

During Drosophila neurogenesis, glial differentiation depends on the expression of glial cells missing (gcm). Understanding how glial fate is achieved thus requires knowledge of the temporal and spatial control mechanisms directing gcm expression. A recent report showed that in the adult bristle lineage, gcm expression is negatively regulated by Notch signaling ( Van De Bor, V.