Butterfly eyespot serial homology: enter the Hox genes

Hox genes modify serial homology patterns in many organisms, exemplified in vertebrates by modification of the axial skeleton and in arthropods by diversification of the body segments. Butterfly wing eyespots also appear in a serial homologous pattern that, in certain species, is subject to local modification. A paper in EvoDevo reports the Hox gene Antp is the earliest known gene to have eyespot-specific expression; however, not all Lepidoptera express Antp in eyespots, suggesting some developmental flexibility

The case of JAK-STAT and EGFR cooperation in oncogenesis

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.Drosophila is proving to be a valuable model for studying aggressive tumors induced by the combined activation of EGFR and JAK-STAT signaling. Here we summarize some of the most recent data showing that tissue damage and the modulation of common pathway regulators are at the heart tumor progression and metastasis.Peer reviewe

From organ selector to cell behavior regulator

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.One of the main contributions of Drosophila to the JAK-STAT field is the study of morphogenesis. JAK-STAT signaling controls the formation of many different structures through surprisingly different morphogenetic behaviors that include induction of cell rearrangements, invagination, folding of tissues, modulation of cell shape, and migration. This variability may be explained by the many transcription factors and signaling molecules STAT regulates at early stages of development. But is STAT just acting as an upstream inducer of morphogenesis or does it have a more direct role in controlling cell behaviors? Here we review what is known about how the canonical phosphorylation of STAT contributes to shaping the embryonic and imaginal structures.This work was supported by the Spanish Ministerio de Investigación Ciencia e Innovación, Consolider, the European Regional Development Fund, and Junta de Andalucía.Peer reviewe

Forces shaping a Hox morphogenetic gene network

The Abdominal-B selector protein induces organogenesis of the posterior spiracles by coordinating an organ-specific gene network. The complexity of this network begs the questions of how it originated and what selective pressures drove its formation. Given that the network likely formed in a piecemeal fashion, with elements recruited sequentially, we studied the consequences of expressing individual effectors of this network in naive epithelial cells.We found that, with exception of the Crossveinless-c (Cv-c) Rho GTPase-activating protein, most effectors exert little morphogenetic effect by themselves. In contrast, Cv-c expression causes cell motility and downregulates epithelial polarity and cell adhesion proteins. These effects differ in cells endogenously expressing Cv-c, which have acquired compensatory mechanisms. In spiracle cells, the down-regulation of polarity and E-cadherin expression caused by Cv-c-induced Rho1 inactivation are compensated for by the simultaneous spiracle up-regulation of guanine nucleotide exchange factor (GEF) proteins, cell polarity, and adhesion molecules. Other epithelial cells that have coopted Cv-c to their morphogenetic gene networks are also resistant to Cv-c's deleterious effects. We propose that cooption of a novel morphogenetic regulator to a selector cascade causes cellular instability, resulting in strong selective pressure that leads that same cascade to recruitmolecules that compensate it. This experimental-based hypothesis proposes how the frequently observed complex organogenetic gene networks are put together.This work was supported by the Spanish Ministerio de Investigación Ciencia e Innovación, Consolider, the European Regional Development Fund, and the Junta de Andalucía.Peer Reviewe

Divergent gene networks select endocrine glands or trachea from a common segmentally repeated precursor in Drosophila

Póster presentado al Joint Spring Meeting of British Society for Developmental Biology and British Society for Cell Biology, celebrado en la Universidad de Warwick (UK) del 17 al 20 de marzo de 2013.The main endocrine organ of Drosophila, the ring gland, is formed by the fusion of the corpora allata (producing Juvenile Hormone), the prothoracic gland (Ecdysone) and the corpus cardiacum (Adipokinetichormone and others). The embryonic origin of the corpus cardiacum from cephalic mesodermal cells has been established, but the origin of the corpora allata (ca) and prothoracic gland (pg) is unknown. We demonstrate that the corpora allata and prothoracic gland develop from cephalic ectodermal cells that in other segments of the body give rise to the trachea. We identify Hox and Vvl as common primary genes required for trachea, corpora allata and prothoracic gland specification; as well as Snail as a specific corpora allata and prothoracic gland gene. Snail controls the ephitelial to mesenchymal transition (EMT) that is one of the major differences between the ring gland and trachea development. We also show that the trachea can be converted into corpora allata or prothoracic gland and viceversa. Our data indicate that endocrine glands and trachea evolved by the divergence of a homologous segmentally repeated structure.Peer Reviewe

Pervasive behavioral effects of microRNA regulation in Drosophila

The effects of microRNA (miRNA) regulation on the genetic programs underlying behavior remain largely unexplored. Despite this, recent work in Drosophila shows that mutation of a single miRNA locus (miR-iab4/iab8) affects the capacity of the larva to correct its orientation if turned upside down (self-righting, SR), suggesting that other miRNAs might also be involved in behavioral control. Here we explore this possibility, studying early larval SR behavior in a collection of 81 Drosophila miRNA mutants covering almost the entire miRNA complement of the late embryo. Unexpectedly, we observe that >40% of all miRNAs tested significantly affect SR time, revealing pervasive behavioral effects of miRNA regulation in the early larva. Detailed analyses of those miRNAs affecting SR behavior (SR-miRNAs) show that individual miRNAs can affect movement in different ways, suggesting that specific molecular and cellular elements are affected by individual miRNA mutations. Furthermore, gene expression analysis shows that the Hox gene Abdominal-B (Abd-B) represents one of the targets deregulated by several SR-miRNAs. Our work thus reveals pervasive effects of miRNA regulation on a complex innate behavior in Drosophila and suggests that miRNAs may be core components of the genetic programs underlying behavioral control in other animals too

JAK/STAT and Hox dynamic interactions in an organogenetic gene cascade

This is an open access article distributed under the terms of the Creative Commons Attribution License.Organogenesis is controlled by gene networks activated by upstream selector genes. During development the gene network is activated stepwise, with a sequential deployment of successive transcription factors and signalling molecules that modify the interaction of the elements of the network as the organ forms. Very little is known about the steps leading from the early specification of the cells that form the organ primordium to the moment when a robust gene network is in place. Here we study in detail how a Hox protein induces during early embryogenesis a simple organogenetic cascade that matures into a complex gene network through the activation of feedback and feed forward interaction loops. To address how the network organization changes during development and how the target genes integrate the genetic information it provides, we analyze in Drosophila the induction of posterior spiracle organogenesis by the Hox gene Abdominal-B (Abd-B). Initially, Abd-B activates in the spiracle primordium a cascade of transcription factors and signalling molecules including the JAK/STAT signalling pathway. We find that at later stages STAT activity feeds back directly into Abd-B, initiating the transformation of the Hox cascade into a gene-network. Focusing on crumbs, a spiracle downstream target gene of Abd-B, we analyze how a modular cis regulatory element integrates the dynamic network information set by Abd-B and the JAK/STAT signalling pathway during development. We describe how a Hox induced genetic cascade transforms into a robust gene network during organogenesis due to the repeated interaction of Abd-B and one of its targets, the JAK/STAT signalling cascade. Our results show that in this network STAT functions not just as a direct transcription factor, but also acts as a >counter-repressor>, uncovering a novel mode for STAT directed transcriptional regulation.JCGH received funding from the Spanish Ministerio de Ciencia y Tecnología BFU2010 www.micinn.es, Ministerio de Economía y Competitividad BFU2013 www.mineco.gob.es, Junta de Andalucía http://www.juntadeandalucia.es/organismos/economiainnovacioncienciayempleo, Programa Consolider and from the European Regional Development Fund.Peer Reviewe

Evidence for the common origin of trachea and endocrine organs from a segmentally repeated ectodermal precursor

Resumen del póster presentado al 23rd European Drosophila Research Conference, celenrado en Barcelona (España) del 16 al 19 de octubre de 2013.Peer Reviewe

Using Drosophila to analyse organogenetic gene network evolution.

Motivation: Cell migration during development is key to the correct development and morphogenesis of animals. This process normally starts with an Epithelial to Mesenchymal Transition (EMT) allowing the normally cohesive and static epithelial cells to migrate. In Drosophila melanogaster the ring gland is formed by three endocrine organs that are specified in different locations and then migrate together: the corpora cardiaca (CC), the corpora allata (CA) and the prothoracic glands (PG). Previous investigations found that CA, PG and trachea can be homeotically transformed into each other, suggesting they all evolved from a metamerically repeated organ. To investigate the lesser known migration of both CA and PG, a reporter gene named sna-rg-eGFP was made using a specific enhancer that activates the expression of the EMT inducer snail (sna) gene in the CA and the PG.This reporter allows us to track the movement of the CA and the PG during their migration. In this way it was possible to identify deletions affecting the migration process. We will present the defects caused by some of these deletions that were found to have a phenotype of apoptosis. Also, we are studying variants altering the sna-rg enhancer as they can provide information on the up-stream regulators of sna activation and CA/PG specification. These showed that, although STAT sites and a fragment called A1 are required for its expression, in the CA the abscence of STAT sites only delays sna-rg expression. This could mean that after its initial activation, the Sna protein could be self regulating or activating other genes to maintain its expression.Methods: For the purpose of finding which gene in the deletion causes the apoptosis phenotype we study with fluorescent microscopy different overlapping deletions to narrow down the suspects. After that we check if the mutation of just one gene causes the phenotype and use UAS/SpaltG4 constructs to find if introducing the gene rescues the phenotype. To study the regulation of the sna-rg enhancer and check if sna is maintaining its own expression we are generating a series of progressively shorter versions of the enhancer regulating GFP and performing RNA in situ hybridization to check the expression of the resulting reporters. This way we study directly the expression directed by the enhancer instead of the protein that is more stable and can last longer

Antagonism versus cooperativity with TALE cofactors at the base of the functional diversification of Hox protein function

International audienceExtradenticle (Exd) and Homothorax (Hth) function as positive transcriptional cofactors of Hox proteins, helping them to bind specifically their direct targets. The posterior Hox protein Abdominal-B (Abd-B) does not require Exd/Hth to bind DNA; and, during embryogenesis, Abd-B represses hth and exd transcription. Here we show that this repression is necessary for Abd-B function, as maintained Exd/Hth expression results in transformations similar to those observed in loss-of-function Abd-B mutants. We characterize the cis regulatory module directly regulated by Abd-B in the empty spiracles gene and show that the Exd/Hth complex interferes with Abd-B binding to this enhancer. Our results suggest that this novel Exd/Hth function does not require the complex to bind DNA and may be mediated by direct Exd/Hth binding to the Abd-B homeodomain. Thus, in some instances, the main positive cofactor complex for anterior Hox proteins can act as a negative factor for the posterior Hox protein Abd-B. This antagonistic interaction uncovers an alternative way in which MEIS and PBC cofactors can modulate Abd-B like posterior Hox genes during development