Patterning plays a crucial role during organogenesis. Axial patterning transforms a single sheet of organ primordial cells to a three dimensional organ by defining the Dorsal-Ventral (DV), Anterior-Posterior (AP) and Proximal-Distal (PD) axis. In the Drosophila eye, DV patterning is the first lineage restriction event, which results in formation of the dorsal and ventral compartments of the eye. Loss-of-function (LOF) of genes involved in DV patterning results in loss of the developing eye field. Understanding the mechanism of this crucial process is far from complete, as there is a need to identify more genetic components of this pathway. We have identified defective proventriculus (dve) as a new member of the DV patterning gene hierarchy using the Drosophila eye model. We have shown that dve is expressed in the dorsal domain of the developing eye imaginal disc and induces a downstream target gene wingless (wg), to promote head specific fate and thereby define the boundary between the eye and the head vertex region. Loss of Wg signaling, within the domain of dve expression results in ectopic eye formation. Ectopic eyes seen in the region that forms the head cuticle and antenna of the adult fly (where dve is not expressed) explains the non-autonomous eyes and dorsal eye enlargements seen by blocking dve mediated regulation of Wg. We propose that the ectopic eyes observed in the dve loss-of-function phenotype is due to downregulation of the highly conserved Wg signaling pathway. Interestingly, change of cell fates also involves the role of highly conserved signaling pathways like Wg, Decapentaplegic (Dpp) and Hedgehog (Hh). We will investigate, if dve can regulate morphogen gradients of these signaling molecules to allocate a fate within the developing eye, head and antennal field. Genetic epistasis shows that dve acts downstream of pannier (pnr) to regulate Wg expression in the dorsal eye.We have characterized the novel role of a K50 homeodomain transcription factor, Dve, in regulating Wg expression in the developing eye. dve has a human ortholog, SATB1 (special AT rich sequence binding protein). We found that Dve expressing cells are the sites for expression of Wg in the dorsal head vertex region of eye imaginal disc. Furthermore, we found that dve is involved in generating the Wg gradient in the eye to determine eye versus head fate. This mechanism may also be conserved in other insects like Lucilia sericata and Phormina regina that display sexual dimorphic traits and differential expression of dve may contribute towards this trait. During development, gene regulation occurs by complex transcriptional networks that drive cell-specific patterns of gene expression. At a molecular level, transcriptional programs are orchestrated by the recruitment of transcription factors (TFs) to enhancer elements or cis-regulatory modules (CRMs) that act as modular units, giving rise to a specific spatial-temporal output of gene expression. Using the enhancer library, a valuable tool to identify enhancers we have been able to identify two eye specific enhancers and one wing specific enhancer of dve. We would further use these tissue-specific enhancer lines of dve to identify the TF binding sites that regulate dve expression. Our studies have provided insights into the molecular genetic mechanism by which dve regulates delineation of an eye versus head fate during development and assigned it to the dorsal eye gene hierarchy as a new DV patterning gene.

An important question in developmental biology is how any three-dimensional organ develops from single monolayer sheet of cells. In multicellular organisms, organogenesis requires axial patterning to determine Antero-Posterior (AP), Dorso-Ventral (DV), and Proximo-Distal (PD) axes. DV patterning marks first lineage restriction event during eye development, any deviation during this event during development results in defective organ formation. We have used Drosophila melanogaster (a.k.a, fruit fly) eye as our model organ as 75% of genetic machinery is conserved between fruit flies and humans and have identified defective proventriculus (dve, a Homeobox gene), an ortholog of SATB-homeobox-1 (special AT-rich sequence binding protein-1 in humans), as a new member of DV- patterning genes hierarchy. We have shown that (1) dve acts downstream of pannier (pnr, a GATA-1 transcription factor), and upstream of wingless (wg), (2) Loss-of-function (LOF) of both dve or pnr results in dorsal eye enlargements, while their Gain-of-function (GOF) suppresses the eye fate, and (3) Furthermore, Wingless (Wg, WNT homolog), downstream target of evolutionarily conserved Hippo growth regulatory pathway, acts downstream of dve in the eye, and exhibits similar eye enlargement or suppression phenotypes upon LOF or GOF. It suggests that like wg, dve also plays an important role in regulating growth. To characterize the function of dve (member of DV patterning pathway) during development, we looked for its interacting partners and found that it interacts antagonistically with Hippo signaling to regulate optimum levels of expression of their common downstream target, Wg, to specify eye versus head fate, during growth and patterning in developing eye. Additionally, GOF of SATB1 (vertebrate ortholog of dve) in the eye also resulted in Wg upregulation and eye suppression. Since GOF of hippo (hpo) triggers cell death, we tested if by blocking cell death by using p35 (anti-apoptotic) exhibits similar phenotypes. We found that eye enlargement phenotype resulting from GOF of hpo in dve domain, is not due to hpo mediated cell death, but by regulating retinal differentiation. Overall, this study presents a model that shows genetic interaction between two unrelated pathways of growth regulation and axial (DV) patterning and have significant bearing on developmental mechanisms. Another focus of this study is to employ Drosophila eye model to study Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disorder characterized by loss of upper and lower motor neurons in central nervous system with no known cure to-date. Mutations in genes like human-Fused in Sarcoma (h-FUS) or cabeza (caz) in Drosophila, have been known to cause ALS in flies. Misexpression of h-FUS-WT (Wild-Type), or FUS mutants FUS-R518K or FUS-R521C in Drosophila eye using GAL4-UAS genetic tool, triggers ALS-mediated neurodegeneration. To understand the mechanism of action, we screened for genetic modifiers and found hippo (hpo), as a genetic modifier. We next tested if this neuroprotective function is exclusive to hpo gene or is dependent on Hippo pathway. We modulated Hippo pathway in FUS-WT or mutant-FUS background and found that downregulation of Hippo pathway, exhibited significant rescue in the eye, but the exact mechanism of action was still unclear. Hippo pathway has been known to activate c-Jun-N-Terminal Kinase (JNK), which is involved in neurodegeneration and cell death. To elucidate the mechanism of action, we modulated JNK signaling in FUS or mutant-FUS background and found that downregulation of JNK signaling also rescued FUS mediated neurodegeneration in eye. This study presents a new model that explains how FUS causes neurodegeneration and has significant bearing on search for future therapeutic targets that can modify neurodegenerative behavior of ALS.

Highlights what we know about the pathways pursued by embryos and evolution, and stresses what we do not yet know.

A comprehensive portrayal of the behaviour genetics of the fruit fly (Drosophila melanogaster) and the methods used in these studies.

Cellular polarization is key to all cellular functions. Our perceptions, which are derived from our senses, depend on the proper cellular polarization of our sense organs, such as the eyes or ears. Much of this book examines the different aspects in cellular polarization and its researched role in the Drosophila, where the first planar cellular polarity (PCP) gene was discovered over 20 years ago. Topics also include: From flies to man: how we are polarized, Marking an embryo work, Cellular polarization at its functional best, Hearing and seeing your environment, and From a cell to an organ. This series represents timely issues in developmental biology. It provides annual reviews of selected topics, written from the perspectives of leading investigators in the field of development. * Presents many various organisms such as flies, fish, frogs and mice * Offers over 40 exceptional illustrations * First of its kind to include new data and detailed models on cell planar polarization

Blood-sucking insects are the vectors of many of the most debilitating parasites of man and his domesticated animals. In addition they are of considerable direct cost to the agricultural industry through losses in milk and meat yields, and through damage to hides and wool, etc. So, not surprisingly, many books of medical and veterinary entomology have been written. Most of these texts are organized taxonomically giving the details of the life-cycles, bionomics, relationship to disease and economic importance of each of the insect groups in turn. I have taken a different approach. This book is topic led and aims to discuss the biological themes which are common in the lives of blood-sucking insects. To do this I have concentrated on those aspects of the biology of these fascinating insects which have been clearly modified in some way to suit the blood-sucking habit. For example, I have discussed feeding and digestion in some detail because feeding on blood presents insects with special problems, but I have not discussed respiration because it is not affected in any particular way by haematophagy. Naturally there is a subjective element in the choice of topics for discussion and the weight given to each. I hope that I have not let my enthusiasm for particular subjects get the better of me on too many occasions and that the subject material achieves an overall balance.

Medical and Veterinary Entomology, Second Edition, has been fully updated and revised to provide the latest information on developments in entomology relating to public health and veterinary importance. Each chapter is structured with the student in mind, organized by the major headings of Taxonomy, Morphology, Life History, Behavior and Ecology, Public Health and Veterinary Importance, and Prevention and Control. This second edition includes separate chapters devoted to each of the taxonomic groups of insects and arachnids of medical or veterinary concern, including spiders, scorpions, mites, and ticks. Internationally recognized editors Mullen and Durden include extensive coverage of both medical and veterinary entomological importance. This book is designed for teaching and research faculty in medical and veterinary schools that provide a course in vector borne diseases and medical entomology; parasitologists, entomologists, and government scientists responsible for oversight and monitoring of insect vector borne diseases; and medical and veterinary school libraries and libraries at institutions with strong programs in entomology. Follows in the tradition of Herm's Medical and Veterinary Entomology The latest information on developments in entomology relating to public health and veterinary importance Two separate indexes for enhanced searchability: Taxonomic and Subject New to this edition: Three new chapters Morphological Adaptations of Parasitic Arthropods Forensic Entomology Molecular Tools in Medical and Veterinary Entomology 1700 word glossary Appendix of Arthropod-Related Viruses of Medical-Veterinary Importance Numerous new full-color images, illustrations and maps throughout