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Mike Levine

Publications and source records attributed to Mike Levine.

12 recordsLinked to original sources
PubMed2006

GATA factors participate in tissue-specific immune responses in Drosophila larvae.

Drosophila responds to infection by producing a broad range of antimicrobial agents in the fat body and more restricted responses in tissues such as the gut, trachea, and malpighian tubules. The regulation of antimicrobial genes in larval fat depends on linked Rel/NF-kappaB and GATA binding sites. Serpent functions as the major GATA transcription factor in the larval fat body. However, the transcriptional regulation of other tissue-specific responses is less well understood. Here, we present evidence that dGATAe regulates antimicrobial gene expression in the midgut. Regulatory regions for antimicrobial genes Diptericin and Metchnikowin require GATA sites for activation in the midgut, where Grain (dGATAc), dGATAd, and dGATAe are expressed in overlapping domains. Ectopic expression of dGATAe in the larval fat body, where it is normally absent, causes dramatic up-regulation of numerous innate immunity and gut genes, as judged by microarray analysis and in situ hybridization. Ectopic dGATAe also causes a host of symptoms reminiscent of hyperactive Toll (Toll(10b)) mutants, but without apparent activation of Toll signaling. Based on this evidence we propose that dGATAe mediates a Toll-independent immune response in the midgut, providing a window into the first and perhaps most ancient line of animal defense.

Animals↗
PubMed2006

FGF signaling delineates the cardiac progenitor field in the simple chordate, Ciona intestinalis.

Comprehensive gene networks in Ciona intestinalis embryos provide a foundation for characterizing complex developmental processes, such as the initial phases of chordate heart development. The basic helix-loop-helix regulatory gene Ci-Mesp is required for activation of cardiac transcription factors. Evidence is presented that Ci-Ets1/2, a transcriptional effector of receptor tyrosine kinase (RTK) signaling, acts downstream from Mesp to establish the heart field. Asymmetric activation of Ets1/2, possibly through localized expression of FGF9, drives heart specification within this field. During gastrulation, Ets1/2 is expressed in a group of four cells descended from two Mesp-expressing founder cells (the B7.5 cells). After gastrulation, these cells divide asymmetrically; the smaller rostral daughters exhibit RTK activation (phosphorylation of ERK) and form the heart lineage while the larger caudal daughters form the anterior tail muscle lineage. Inhibition of RTK signaling prevents heart specification. Targeted inhibition of Ets1/2 activity or FGF receptor function also blocks heart specification. Conversely, application of FGF or targeted expression of constitutively active Ets1/2 (EtsVp16) cause both rostral and caudal B7.5 lineages to form heart cells. This expansion produces an unexpected phenotype: transformation of a single-compartment heart into a functional multicompartment organ. We discuss these results with regard to the development and evolution of the multichambered vertebrate heart.

Animals↗
PubMed2006

Computational models for neurogenic gene expression in the Drosophila embryo.

The early Drosophila embryo is emerging as a premiere model system for the computational analysis of gene regulation in development because most of the genes, and many of the associated regulatory DNAs, that control segmentation and gastrulation are known. The comprehensive elucidation of Drosophila gene networks provides an unprecedented opportunity to apply quantitative models to metazoan enhancers that govern complex patterns of gene expression during development. Models based on the fractional occupancy of defined DNA binding sites have been used to describe the regulation of the lac operon in E. coli and the lysis/lysogeny switch of phage lambda. Here, we apply similar models to enhancers regulated by the Dorsal gradient in the ventral neurogenic ectoderm (vNE) of the early Drosophila embryo. Quantitative models based on the fractional occupancy of Dorsal, Twist, and Snail binding sites raise the possibility that cooperative interactions among these regulatory proteins mediate subtle differences in the vNE expression patterns. Variations in cooperativity may be attributed to differences in the detailed linkage of Dorsal, Twist, and Snail binding sites in vNE enhancers. We propose that binding site occupancy is the key rate-limiting step for establishing localized patterns of gene expression in the early Drosophila embryo.

Animals↗
PubMed2006

Evolution of the ventral midline in insect embryos.

The ventral midline is a source of signals that pattern the nerve cord of insect embryos. In dipterans such as the fruitfly Drosophila melanogaster (D. mel.) and the mosquito Anopheles gambiae (A. gam.), the midline is narrow and spans just 1-2 cells. However, in the honeybee, Apis mellifera (A. mel.), the ventral midline is broad and encompasses 5-6 cells. slit and other midline-patterning genes display a corresponding expansion in expression. Evidence is presented that this difference is due to divergent cis regulation of the single-minded (sim) gene, which encodes a bHLH-PAS transcription factor essential for midline differentiation. sim is regulated by a combination of Notch signaling and a Twist (Twi) activator gradient in D. mel., but it is activated solely by Twi in A. mel. We suggest that the Twi-only mode of regulation--and the broad ventral midline--represents the ancestral form of CNS patterning in Holometabolous insects.

Animals↗
PubMed2005

The Drosophila microRNA iab-4 causes a dominant homeotic transformation of halteres to wings.

The Drosophila Bithorax Complex encodes three well-characterized homeodomain proteins that direct segment identity, as well as several noncoding RNAs of unknown function. Here, we analyze the iab-4 locus, which produces the microRNAs iab-4-5p and iab-4-3p. iab-4 is analogous to miR-196 in vertebrate Hox clusters. Previous studies demonstrate that miR-196 interacts with the Hoxb8 3' untranslated region. Evidence is presented that miR-iab-4-5p directly inhibits Ubx activity in vivo. Ectopic expression of mir-iab-4-5p attenuates endogenous Ubx protein accumulation and induces a classical homeotic mutant phenotype: the transformation of halteres into wings. These findings provide the first evidence for a noncoding homeotic gene and raise the possibility that other such genes occur within the Bithorax complex. We also discuss the regulation of mir-iab-4 expression during development.

3' Untranslated Regions↗
PubMed2005

Surfing with the tunicates into the post-genome era.

This year is the centenary of Edward G. Conklin's signal findings in embryology: the elucidation of complete cell lineages and the discovery of localized maternal determinants. Conklin used ascidian embryos to elucidate universal principles in embryology. A century later, ascidians, or sea squirts, have not only entered the post-genome era, but in many ways are leading the way to the promise of a "systems-level" understanding of complex processes such as notochord formation, neurogenesis, and even behavior.

Animals↗
PubMed2005

A saturation screen for cis-acting regulatory DNA in the Hox genes of Ciona intestinalis.

A screen for the systematic identification of cis-regulatory elements within large (>100 kb) genomic domains containing Hox genes was performed by using the basal chordate Ciona intestinalis. Randomly generated DNA fragments from bacterial artificial chromosomes containing two clusters of Hox genes were inserted into a vector upstream of a minimal promoter and lacZ reporter gene. A total of 222 resultant fusion genes were separately electroporated into fertilized eggs, and their regulatory activities were monitored in larvae. In sum, 21 separable cis-regulatory elements were found. These include eight Hox linked domains that drive expression in nested anterior-posterior domains of ectodermally derived tissues. In addition to vertebrate-like CNS regulation, the discovery of cis-regulatory domains that drive epidermal transcription suggests that C. intestinalis has arthropod-like Hox patterning in the epidermis.

Animals↗
PubMed2004

Different combinations of gap repressors for common stripes in Anopheles and Drosophila embryos.

Drosophila segmentation is governed by a well-defined gene regulation network. The evolution of this network was investigated by examining the expression profiles of a complete set of segmentation genes in the early embryos of the mosquito, Anopheles gambiae. There are numerous differences in the expression profiles as compared with Drosophila. The germline determinant Oskar is expressed in both the anterior and posterior poles of Anopheles embryos but is strictly localized within the posterior plasm of Drosophila. The gap genes hunchback and giant display inverted patterns of expression in posterior regions of Anopheles embryos, while tailless exhibits an expanded pattern as compared with Drosophila. These observations suggest that the segmentation network has undergone considerable evolutionary change in the dipterans and that similar patterns of pair-rule gene expression can be obtained with different combinations of gap repressors. We discuss the evolution of separate stripe enhancers in the eve loci of different dipterans.

Animals↗
PubMed2004

Visualization of trans-homolog enhancer-promoter interactions at the Abd-B Hox locus in the Drosophila embryo.

The Hox gene Abdominal-B (Abd-B) controls the morphogenesis of posterior abdominal segments in Drosophila. Expression is regulated by a series of 3' enhancers that are themselves transcribed. RNA FISH was used to visualize nascent transcripts associated with coding and noncoding regions of Abd-B in developing embryos. Confocal imaging suggests that distal enhancers often loop to the Abd-B promoter region. Surprisingly, enhancers located on one chromosome frequently associate with the Abd-B transcription unit located on the other homolog. These trans-homolog interactions can be interpreted as the direct visualization of a genetic phenomenon known as transvection, whereby certain mutations in Abd-B can be rescued in trans by the other copy of the gene. A 10 kb sequence in the 3' flanking region mediates tight pairing of Abd-B alleles, thereby facilitating trans looping of distal enhancers. Such trans-homolog interactions might be a common mechanism of gene regulation in higher metazoans.

Alleles↗
PubMed2004

A genome analysis of endoreplication in the Drosophila ovary.

Gene amplification is used by follicle cells to increase the copy number of Drosophila chorion genes, which encode structural components of the eggshell. A new study by Claycomb et al. in this issue of Developmental Cell raises the possibility that gene amplification might also be used for the developmental patterning of the egg chamber and oocyte.

Animals↗
PubMed2003

Mike Levine.

Explore the source record for details and available documents.

Developmental Biology↗