James Castelli-Gair Hombrı́a

Centro Andaluz de Biología del Desarrollo

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Sol Sotillos

Centro Andaluz de Biología del Desarrollo

José Manuel Espinosa

Centro Andaluz de Biología del Desarrollo

Carlos Sánchez-Higueras

Centro Andaluz de Biología del Desarrollo

Stephen Brown

University of the Free State

María Luisa Rivas

Consejo Superior de Investigaciones Científicas

Mario Aguilar‐Aragon

Instituto de Neurociencias

Antonio Garcı́a-Bellido

Centro de Biología Molecular Severo Ochoa

Martin P. Zeidler

University of Sheffield

Nan Hu

Shenyang Agricultural University

Daniel Rodríguez

University of Fribourg

Cooperative Institutions

Consejo Superior de Investigaciones Científicas

Universidad Pablo de Olavide

Centro Andaluz de Biología del Desarrollo

University of Cambridge

Universidad Autónoma de Madrid

Centro de Biología Molecular Severo Ochoa

Junta de Andalucía

Centre National de la Recherche Scientifique

Columbia University

Howard Hughes Medical Institute

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Interplay between the ABD-B Hox protein and its downstream target STAT converts the selection gene cascade into an organogenetic gene network

Pedro Borges Pinto José Manuel Espinosa María Luisa Rivas James Castelli‐Gair Hombría

Resumen del trabajo presentado al Cost Meeting: Hox and Tale transcription factors in Development and Disease celebrado en Egmond aan Zee (NL) del 2 al 4 de octubre de 2013.

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Positive and negative cis-regulatory elements in the bithoraxoid region of the Drosophila Ultrabithorax gene

MGG Molecular & General Genetics (1992)

James Castelli‐Gair Hombría M. P. Capdevila José Luis Micol Antonio Garcı́a-Bellido

Ultrabithorax

Compartment (ship)

10.1007/bf00283837

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Citations (13)

Author Reply to Peer Reviews of Specification of the endocrine primordia controlling insect moulting and metamorphosis by the JAK/STAT signalling pathway

Mar García-Ferrés Carlos Sánchez-Higueras José Manuel Espinosa James Castelli‐Gair Hombría

Signalling

Signalling pathways

10.15252/rc.2023359043

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Transvection in the Drosophila Ultrabithorax gene: a Cbx1 mutant allele induces ectopic expression of a normal allele in trans.

Genetics (1990)

James Castelli‐Gair Hombría José Luis Micol Antonio Garcı́a-Bellido

Abstract In wild-type Drosophila melanogaster larvae, the Ultrabithorax (Ubx) gene is expressed in the haltere imaginal discs but not in the majority of cells of the wing imaginal discs. Ectopic expression of the Ubx gene in wing discs can be elicited by the presence of Contrabithorax (Cbx) gain-of-function alleles of the Ubx gene or by loss-of-function mutations in Polycomb (Pc) or in other trans-regulatory genes which behave as repressors of Ubx gene activity. Several Ubx loss-of-function alleles cause the absence of detectable Ubx proteins (UBX) or the presence of truncated UBX lacking the homeodomain. We have compared adult wing phenotypes with larval wing disc UBX patterns in genotypes involving double mutant chromosomes carrying in cis one of those Ubx mutations and the Cbx1 mutation. We show that such double mutant genes are (1) active in the same cells in which the single mutant Cbx1 is expressed, although they are unable to yield functional proteins, and (2) able to induce ectopic expression of a normal homologous Ubx allele in a part of the cells in which the single mutant Cbx1 is active. That induction is conditional upon pairing of the homologous chromosomes (the phenomenon known as transvection), and it is not mediated by UBX. Depletion of Pc gene products by Pc3 mutation strongly enhances the induction phenomenon, as shown by (1) the increase of the number of wing disc cells in which induction of the homologous allele is detectable, and (2) the induction of not only a paired normal allele but also an unpaired one.

Ultrabithorax

Ectopic expression

Null allele

10.1093/genetics/126.1.177

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Citations (32)

An efficient approach to isolate STAT regulated enhancers uncovers STAT92E fundamental role in Drosophila tracheal development

Developmental Biology (2010)

Sol Sotillos José Manuel Espinosa Filippo Foglia Nan Hu James Castelli‐Gair Hombría

The ventral veinless (vvl) and trachealess (trh) genes are determinants of the Drosophila trachea. Early in development both genes are independently activated in the tracheal primordia by signals that are ill defined. Mutants blocking JAK/STAT signaling at any level do not form a tracheal tree suggesting that STAT92E may be an upstream transcriptional activator of the early trachea determinants. To test this hypothesis we have searched for STAT92E responsive enhancers activating the expression of vvl and trh in the tracheal primordia. We show that STAT92E regulated enhancers can be rapidly and efficiently isolated by focusing the analysis on genomic regions with clusters of putative STAT binding sites where at least some of them are phylogenetically conserved. Detailed analysis of a vvl early tracheal enhancer shows that non-conserved sites collaborate with conserved sites for enhancer activation. We find that STAT92E regulated enhancers can be located as far 60 kb from the promoters. Our results indicate that vvl and trh are independently activated by STAT92E which is the most important transcription factor required for trachea specification.

Enhancer trap

Primordium

Conserved sequence

Enhancer RNAs

10.1016/j.ydbio.2010.02.015

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Citations (31)

Plasticity of Drosophila Stat DNA binding shows an evolutionary basis for Stat transcription factor preferences

EMBO Reports (2008)

María Luisa Rivas Laura Cobreros Martin P. Zeidler James Castelli‐Gair Hombría

In vertebrates, seven signal transducer and activator of transcription (STAT) proteins bind to palindromic sites separated by spacers of two or three nucleotides (STAT1), four nucleotides (STAT6) or three nucleotides (STAT2 to STAT5a/b). This diversity of binding sites provides specificity to counter semiredundancy and was thought to be a recent evolutionary acquisition. Here, we examine the natural DNA‐binding sites of the single Drosophila Stat and show that this is not the case. Rather, Drosophila Stat92E is able to bind to and activate target gene expression through both 3 n and 4 n spaced sites. Our experiments indicate that Stat92E has a higher binding affinity for 3 n sites than for 4 n sites and suggest that the levels of target gene expression can be modulated by insertion and/or deletion of single bases. Our results indicate that the ancestral STAT protein had the capacity to bind to 3 n and 4 n sites and that specific STAT binding preferences evolved with the radiation of the vertebrate STAT family.

STAT2

STAT4

STAT6

STAT1

DNA binding site

Transcription

10.1038/embor.2008.170

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Citations (35)

In vivo Hox binding specificity revealed by systematic changes to a single cis regulatory module

Nature Communications (2019)

Carlos Sánchez-Higueras Chaitanya Rastogi Roumen Voutev Harmen J. Bussemaker Richard S. Mann

Abstract Hox proteins belong to a family of transcription factors with similar DNA binding specificities that control animal differentiation along the antero-posterior body axis. Hox proteins are expressed in partially overlapping regions where each one is responsible for the formation of particular organs and structures through the regulation of specific direct downstream targets. Thus, explaining how each Hox protein can selectively control its direct targets from those of another Hox protein is fundamental to understand animal development. Here we analyse a cis regulatory module directly regulated by seven different Drosophila Hox proteins and uncover how different Hox class proteins differentially control its expression. We find that regulation by one or another Hox protein depends on the combination of three modes: Hox-cofactor dependent DNA-binding specificity; Hox-monomer binding sites; and interaction with positive and negative Hox-collaborator proteins. Additionally, we find that similar regulation can be achieved by Amphioxus orthologs, suggesting these three mechanisms are conserved from insects to chordates.

10.1038/s41467-019-11416-1

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Citations (36)

Cell Signalling: Combining Pathways for Diversification and Reproducibility

Current Biology (2016)

James Castelli‐Gair Hombría Acaimo González‐Reyes

Signalling

Signalling pathways

10.1016/j.cub.2016.08.070

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Citations (1)

Searching for genes required for Drosophila ring gland development

Mar Silvia García Ferrés James Castelli‐Gair Hombría

Resumen del trabajo presentado en el European Developmental Biology Congress, celebrado en Alicante (Espana), del 23 al 26 de octubre de 2019

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Genetic analysis of transvection effects involving cis-regulatory elements of the Drosophila Ultrabithorax gene.

Genetics (1990)

José Luis Micol James Castelli‐Gair Hombría Antonio Garcı́a-Bellido

Abstract The Ultrabithorax (Ubx) gene of Drosophila melanogaster contains two functionally distinguishable regions: the protein-coding Ubx transcription unit and, upstream of it, the transcribed but nonprotein-coding bxd region. Numerous recessive, partial loss-of-function mutations which appear to be regulatory mutations map within the bxd region and within the introns of the Ubx transcription unit. In addition, mutations within the Ubx unit exons are known and most of these behave as null alleles. Ubx1 is one such allele. We have confirmed that, although the Ubx1 allele does not produce detectable Ubx proteins (UBX), it does retain other genetic functions detectable by their effects on the expression of a paired, homologous Ubx allele, i.e., by transvection. We have extended previous analyses made by E. B. Lewis by mapping the critical elements of the Ubx gene which participate in transvection effects. Our results show that the Ubx1 allele retains wild-type functions whose effectiveness can be reduced (1) by additional cis mutations in the bxd region or in introns of the Ubx transcription unit, as well as (2) by rearrangements disturbing pairing between homologous Ubx genes. Our results suggest that those remnant functions in Ubx1 are able to modulate the activity of the allele located in the homologous chromosome. We discuss the normal cis regulatory role of these functions involved in trans interactions between homologous Ubx genes, as well as the implications of our results for the current models on transvection.

Ultrabithorax

Null allele

Transcription

Coding region

10.1093/genetics/126.2.365

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Citations (15)