Homeotic genes autonomously specify one aspect of pattern in the Drosophlla mesoderm

Greig, Stephen; Akam, Michael

doi:10.1038/362630a0

Cited by 160 publications

(95 citation statements)

References 15 publications

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“…Since Numb appears to influence cell fate decisions in mesoderm as well, 2 we wanted to see if the mutations that we were examining in neural development have a similar effect during mesoderm development. To assay for this, the UAS-Numb wild-type and mutant lines were crossed to the twist-GAL4;24B-GAL4 line (27,33), which drives Numb expression throughout the 2 M. Park, L. Yaich, and R. Bodmer, unpublished observations. Semi-lethal (ϩϩϩϩ) UAS-Numbϩ (7) Viable (ϩϩϩϩ) UAS-Numbϩ (10) Semi-lethal (ϩϩϩϩ) UAS-Numbϩ (11) Viable (ϩϩϩ) UAS-Numbϩ (12) Semi-lethal (ϩϩϩϩ) UAS-Numb (R171Q) (1) Semi-lethal (ϩϩϩϩ) UAS-Numb (R171Q) (2) Viable (ϩϩϩϩ) UAS-Numb (R171Q) (5) Semi-lethal (ϩϩϩϩ) UAS-Numb (R171Q) (7) Semi-lethal (ϩϩϩϩ) UAS-Numb (S148A) (1) Viable (ϩϩϩϩ) UAS-Numb (S148A) (3) Viable (ϩϩϩϩ) UAS-Numb (S148A) (5) Semi-lethal (ϩϩϩϩ) UAS-Numb (S148A) (6) Viable (ϩϩϩϩ) UAS-Numb (S148A) (7) Pupal lethal (ϩϩϩϩ) UAS-Numb (F149L) (1) Viable (ϩ) UAS-Numb (F149L) (4) Viable (ϩϩ) UAS-Numb (F149L) (6) Viable (ϩϩ) UAS-Numb (F149L) (8) Viable (ϩϩϩ) a Percentage of bristle loss observed when crossed to 189-GAL4: (ϩ) 0 -25% macrochaetae missing, (ϩϩ) 26 -50% macrochaetae missing, (ϩϩϩ) 51-75% macrochaetae missing, and (ϩϩϩϩ) 76 -100% macrochaetae missing.…”

Section: Resultsmentioning

confidence: 99%

Functional Analysis of the Numb Phosphotyrosine-binding Domain Using Site-directed Mutagenesis

Yaich

Ooi

Park

et al. 1998

Journal of Biological Chemistry

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The Numb protein is involved in cell fate determination during Drosophila neural development. Numb has a protein domain homologous to the phosphotyrosinebinding domain (PTB) in the adaptor protein Shc. In Shc, this domain interacts with specific phosphotyrosine containing motifs on receptor tyrosine kinases and other signaling molecules. Residues N-terminal to the phosphotyrosine are also crucial for phosphopeptide binding to the Shc PTB domain. Several amino acid residues in Shc have been implicated by site-directed mutagenesis to be critical for Shc binding to receptor tyrosine kinases. We have generated homologous mutations in Numb to test whether, in vivo, these changes affect Numb function during Drosophila sensory organ development. Two independent amino acid changes that interfere with Shc binding to phosphotyrosine residues do not affect Numb activity in vivo. In contrast, a mutation shown to abrogate the ability of the Shc PTB domain to bind residues upstream of the phosphotyrosine virtually eliminates Numb function. Similar results were observed in vitro by examining the binding of the Numb PTB domain to proteins from Schneider S2 cells. Our data confirm the importance of the PTB domain for Numb function but strongly suggest that the Numb PTB domain is not involved in phosphotyrosine-dependent interactions.

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Section: Resultsmentioning

confidence: 99%

Functional Analysis of the Numb Phosphotyrosine-binding Domain Using Site-directed Mutagenesis

Yaich

Ooi

Park

et al. 1998

Journal of Biological Chemistry

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“…Transgenes for enhancer assays were recombined with the loss-of-function EMS-induced allele sna 18 (sna IIG05 ) (Grau et al 1984) and the hypomorphic sna V2 allele. The mata4-GAL4:VP16 (V32) stock was provided by Daniel St. Johnston, the twi-Gal4 stock was from Michael Akam (Greig and Akam 1993), and the UAS-TCF-DN stock was generated by the Hans Clevers laboratory (van de Wetering et al 1997).…”

Section: Drosophila Strainsmentioning

confidence: 99%

A conserved role for Snail as a potentiator of active transcription

et al. 2014

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The transcription factors of the Snail family are key regulators of epithelial–mesenchymal transitions, cell morphogenesis, and tumor metastasis. Since its discovery in Drosophila ∼25 years ago, Snail has been extensively studied for its role as a transcriptional repressor. Here we demonstrate that Drosophila Snail can positively modulate transcriptional activation. By combining information on in vivo occupancy with expression profiling of hand-selected, staged snail mutant embryos, we identified 106 genes that are potentially directly regulated by Snail during mesoderm development. In addition to the expected Snail-repressed genes, almost 50% of Snail targets showed an unanticipated activation. The majority of “Snail-activated” genes have enhancer elements cobound by Twist and are expressed in the mesoderm at the stages of Snail occupancy. Snail can potentiate Twist-mediated enhancer activation in vitro and is essential for enhancer activity in vivo. Using a machine learning approach, we show that differentially enriched motifs are sufficient to predict Snail's regulatory response. In silico mutagenesis revealed a likely causative motif, which we demonstrate is essential for enhancer activation. Taken together, these data indicate that Snail can potentiate enhancer activation by collaborating with different activators, providing a new mechanism by which Snail regulates development.

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“…Fly strains used in this study: ut H599 , ut H76 and ut M638 (Salzberg et al, 1994); vvl GA3 (de-Celis et al, 1995); 5′F:2.6 atonal (ato)-lacZ ; A1-2-29 (Bier et al, 1989); A101 neuralized (neu)-lacZ (Huang et al, 1991); UAS-abd-A (Greig and Akam, 1993), armadillo (arm)-Gal4 vvl GA3 /TM3, Sb ftz-lacZ (this work); ato-Gal4 vvl GA3 / TM6,Tb P[w + , Tb P[w + , (FlyBase, 1999).…”

Section: Fly Strainsmentioning

confidence: 99%

Multiple roles foru-turn/ventral veinlessin the development ofDrosophilaPNS

2003

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Most of the cells in the embryonic peripheral nervous system (PNS) of Drosophila are born in their final location. One known exception is the group of lateral chordotonal organs (lch5) whose precursors form in a dorsal position, yet the mature organs are located in the lateral PNS cluster. Mutations in the u-turn (ut) locus perturb the localization of lch5 neurons and result in a 'dorsal chordotonals' phenotype. We show that ut is allelic to ventral veinless (vvl), also known as drifter. VVL, a POU-domain transcription factor, has been shown to participate in the development of tracheae and CNS in the embryo, and in wing development in the adult; however, its role in PNS development has not been described. Characterization of the 'dorsal chordotonals' phenotype of vvl mutant embryos revealed that in the absence of VVL, cell fates within the lch5 lineage are determined properly and the entire organ is misplaced.Based on the positions of lch5 cells relative to each other in mutant embryos, and in normal embryos at different developmental stages, we propose a two-step model for lch5 localization. lch5 organs must first rotate to assume a correct polarity and are then stretched ventrally to their final position. In this process, VVL function is required in the ectoderm and possibly in the lch5 organs too.VVL is also expressed in developing external sensory organs in the embryo and in the adult. In the embryo, loss of VVL function results in increased apoptosis in specific es organs. Analysis of vvl mutant clones in adults revealed a requirement for VVL in the control of cell number within the bristle lineage.

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Homeotic genes autonomously specify one aspect of pattern in the Drosophlla mesoderm

Cited by 160 publications

References 15 publications

Functional Analysis of the Numb Phosphotyrosine-binding Domain Using Site-directed Mutagenesis

Functional Analysis of the Numb Phosphotyrosine-binding Domain Using Site-directed Mutagenesis

A conserved role for Snail as a potentiator of active transcription

Multiple roles foru-turn/ventral veinlessin the development ofDrosophilaPNS

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