Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye

Basler, Konrad; Christen, Bea; Hafen, Ernst

doi:10.1016/0092-8674(91)90262-w

Cited by 240 publications

(158 citation statements)

References 49 publications

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“…In wild type, this inhibition is presumably overridden in the R7 precursor by the boss-and sevenless-mediated signal. This model is consistent with the observations that nonspecific expression of boss (22) and overexpression of an activated form of sevenless (23) lead to phenotypes that are similar to that seen in sxt/sxt flies. Presumably, in these cases, ectopic activation of the receptor can overcome the inhibitory effects of sxt in the cone-cell precursors.…”

Section: Discussionsupporting

confidence: 79%

Neuronal development in the Drosophila retina: the sextra gene defines an inhibitory component in the developmental pathway of R7 photoreceptor cells.

Rogge

Cagan

Majumdar

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Mutations in a gene called sextra (sxt) have been isolated. Loss of one copy of sxt promotes R7 photoreceptor cell development in a genetically sensitized background, while loss of both copies results in precursors of non-neuronal cone cells transforming into R7 cells. The requirement for sxt function is cell-autonomous. The transformation of cone-cell precursors into R7 cells occurs independently of the sevenless signal. However, the R7 precursor becomes neuronal in an sxt/sxt mutant only in a wild-type sevenless background. The genetic analysis of sxt suggests that it plays an inhibitory role, preventing cone cells from becoming neuronal. Additionally, sxt functions in R7 precursors, but the sevenless sial is essential for specification of this fate, since oss of sextra alone is unable to impart a neural fate to this cell.Characterization of a set ofgenes controlling R7 development has provided much insight into the process of induction and signal transduction (1)(2)(3)(4). Genetic and molecular analysis of sevenless (sev) (5-8) and bride of sevenless (boss) (9, 10) has demonstrated that R8 induces a neighboring cell to take on the R7 fate (9). In boss or sev mutants, R7 cells are missing within the eye. While the boss protein, a membrane-bound ligand, is required in the inducing R8 cell for normal R7 development (11), the sev gene encodes a tyrosine kinase receptor required in the R7 precursor for it to assume an R7 fate (12, 13). The boss protein has been shown to bind directly to the sevenless protein (11), initiating a molecular cascade that causes development of the R7 neuron.Recently, two more genes, Son of sevenless (Sos) 78C/D were mated to either sxtlu6I/sxtBJ6' or sxtRI6I,bossl/ sxtMu6l,bossl males. Progeny from these crosses were irradiated with -y-rays (1200 rads; 1 rad = 0.01 Gy) between 24 and 48 hr of development. Mosaic eyes were generated at a frequency of -0.01. Histology. Preparation of samples for transmission electron microscopy (TEM) was essentially as described (19), except that uranyl acetate staining en bloc was omitted. The sections were stained for 30 min with uranyl acetate and 10 min with lead citrate and were analyzed on a Phillips 300 electron microscope operating at 60 kV. For light-level microscopy, the fixation conditions were modified as described (9). To facilitate scoring of pigment granules, flies were exposed to bright light for 10 min before dissection. Cobalt sulfide staining was done as described (4).Immunohistochemistry. Adult heads were dissected into halves and fixed for 1 hr in 0.8% glutaraldehyde in phosphatebuffered saline. The retinas were transferred to fresh fixative, dissected out of the surrounding cuticle, allowed to fix for another 30 min, stained with antibodies (8), and embedded for sectioning (9). Eye imaginal discs were stained with monoclonal antibody (mAb) 22C10 and processed for TEM (11). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accord...

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Section: Discussionsupporting

confidence: 79%

Neuronal development in the Drosophila retina: the sextra gene defines an inhibitory component in the developmental pathway of R7 photoreceptor cells.

Rogge

Cagan

Majumdar

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…P element-mediated germ-line transformation was performed as described (26). The constructs were injected into y w embryos.…”

Section: Methods Ethyl Methanesulfonate (Ems) Mutagenesis and Analysimentioning

confidence: 99%

PDK1 regulates growth through Akt and S6K in Drosophila

Rintelen

Stocker

Thomas

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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125

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The insulin͞insulin-like growth factor-1 signaling pathway promotes growth in invertebrates and vertebrates by increasing the levels of phosphatidylinositol 3,4,5-triphosphate through the activation of p110 phosphatidylinositol 3-kinase. Two key effectors of this pathway are the phosphoinositide-dependent protein kinase 1 (PDK1) and Akt͞PKB. Although genetic analysis in Caenorhabditis elegans has implicated Akt as the only relevant PDK1 substrate, cell culture studies have suggested that PDK1 has additional targets. Here we show that, in Drosophila, dPDK1 controls cellular and organism growth by activating dAkt and S6 kinase, dS6K. Furthermore, dPDK1 genetically interacts with dRSK but not with dPKN, encoding two substrates of PDK1 in vitro. Thus, the results suggest that dPDK1 is required for dRSK but not dPKN activation and that it regulates insulin-mediated growth through two main effector branches, dAkt and dS6K.

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“…Whereas ebi dominantly suppressed R7 development induced by the activated EGFR expressed in the R7 equivalence group under the control of the sev enhancer (sev-Tor D Egfr) ( Fig. 3 (Basler et al 1991; data not shown), or activated forms of Ras, Raf, and MAPK (data not shown). Hence, ebi is required for the transformation of cone cell precursors into R7 neurons by the activated EGFR.…”

Section: Ebi Is Required For R7 Developmentmentioning

confidence: 99%

ebi regulates epidermal growth factor receptor signaling pathways in Drosophila

Dong¹,

Tsuda²,

Zavitz³

et al. 1999

Genes & Development

118

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ebi regulates the epidermal growth factor receptor (EGFR) signaling pathway at multiple steps in Drosophila development. Mutations in ebi and Egfr lead to similar phenotypes and show genetic interactions. However, ebi does not show genetic interactions with other RTKs (e.g., torso) or with components of the canonical Ras/MAP kinase pathway. ebi encodes an evolutionarily conserved protein with a unique amino terminus, distantly related to F-box sequences, and six tandemly arranged carboxy-terminal WD40 repeats. Epidermal growth factor receptors (EGFRs) have a central role in vertebrate and invertebrate development (for review, see van der Geer et al. 1994;Wassarman et al. 1995;Freeman 1998). Biochemical studies largely in mammalian systems and genetic studies in Caenorhabditis elegans and Drosophila have led to a detailed description of the signal transduction pathways elicited by activation of the EGFR (for review, see Kayne and Sternberg 1995; Schwietzer and Shilo 1997). These include the Ras/MAP kinase (MAPK), Ca 2+ , and phosphatidyl inositol-dependent signaling pathways (for review, see Kazlauskas 1994). In Drosophila, the Ras/MAP kinase cascade is the prominent signaling pathway triggered by the EGFR. Two other fly receptor tyrosine kinases (RTKs) that control patterning and cell fate specification, Torso (for review, see Duffy and Perrimon 1994) and Sevenless (Sev) (for review, see Zipursky and Rubin 1994), do so largely, if not exclusively, through activation of this pathway.The development of the R7 photoreceptor neuron in the fly eye has proved to be a system amenable to detailed genetic dissection of RTK signaling pathways (Wassarman et al. 1995). Whereas the Sev RTK is required for the development of R7 only, EGFR is essential for the development of most, if not all, cells, including R7 (for review, see Freeman 1996a). This dual RTK requirement is intriguing. Constitutively active overexpressed forms of both Sev and EGFR are sufficient to induce R7 development. Furthermore, overexpression of Spitz, a ligand for EGFR, can partially rescue R7 development in a sev null mutant background. These findings have led Freeman (1996b) to propose that signals from Sev and EGFR are qualitatively equivalent. This is consistent with previous findings that overexpression of activated forms of proteins in the Ras/MAP kinase pathway induce receptor-independent R7 development (Fortini et al. 1992;Dickson et al. 1992a;Brunner et al. 1994). These observations support the view that activation of the Ras/MAPK pathway is sufficient to induce R7 development during normal development.The activities of three transcription factors are modulated by the MAPK signaling pathway in the R7 precursor cell. Two ETS-domain-containing transcription factors, Yan and Pointed, are direct targets of MAPK phosphorylation: Pointed is activated by phosphorylation and promotes R7 induction (O'Neil et al. 1994), whereas Yan is inhibited by phosphorylation and acts as a transcriptional repressor (Rebay and Rubin 1995). Inactivation of a second rep...

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Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye

Cited by 240 publications

References 49 publications

Neuronal development in the Drosophila retina: the sextra gene defines an inhibitory component in the developmental pathway of R7 photoreceptor cells.

Neuronal development in the Drosophila retina: the sextra gene defines an inhibitory component in the developmental pathway of R7 photoreceptor cells.

PDK1 regulates growth through Akt and S6K in Drosophila

ebi regulates epidermal growth factor receptor signaling pathways in Drosophila

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