Gut patterning and PANcreas development in evolution and disease: a TRAnsCriptomic approach

Summary

Many genes that have been shown to cause diseases were originally identified because of their role in embryonic development, but were subsequently shown to be also important in the postnatal control of cell growth and differentiation. This is the case of many transcription factors (TF) among which the ParaHox gene Xlox, whose mammalian homolog, Pdx1, is well known for its role in specification of the pancreas, and subsequent formation and maintenance of pancreatic beta-cells. Pdx1 is a causal factor in the development of diabetes, wherein there is a deficiency in insulin production of beta-cells within the pancreas. Moreover, mis-expression of Pdx1 is commonly seen in intestinal disorders such as Crohn’s disease. Here we propose to combine analyses in the highly simple but phylogenetically relevant sea urchin embryo and sea star embryo models with developmentally targeted mouse transcriptome data to characterize regulatory connections that are downstream of the disease-related Xlox/Pdx1 transcription factor.

What we do

We are coordinator of the project and Operating unit SZN and will perform all manipulations and analyses in sea urchin and sea star embryos and all bioinformatic analyses and evolutionary comparisons.

Partners

Stazione Zoologica Anton Dohrn, Napoli; Laboratorio di Medicina Molecolare e Genomica, Università degli Studi di Salerno.

Research Area

Organismal Biology

Project Lifetime

April 2014 to December 2015

SZN Role

Coordinator

Principal Investigator

Maria I. Arnone

Funding Institution

MIUR Progetti Premiali (DLGS 213/99)

Contribution to SZN

€169.143,00 (MIUR contribution)

Publications

Annunziata R and Arnone MI (2014). A dynamic network of regulatory interactions explains ParaHox gene control of gut patterning in the sea urchin embryo. Development 141: 2462-72.

Perillo M, Wang YJ, Leach SD and Arnone MI. Specification and differentiation of pancreatic, acinar-like cells in the sea urchin embryo and larva. Submitted to Development.

Meet the team

Maria I. Arnone, primo ricercatore
Rossella Annunziata, postdoc
Claudia Cuomo, PhD student
Elijah Lowe, postdoc

Non-Coding RNA Explosion: Novel Implications in Neurotrophin Biology
FIRB, MIUR-Cineca

Summary

The main focus of the project is the identification of non-coding RNAs (ncRNA) that regulate the expression of Neurotrophins (NT) and NT receptors (NTR). ncRNAs are a novel class of regulatory molecules that have been shown to be involved in almost all biological phenomena, including development and physiology of the nervous system.
Neurotrophins (NT) (BDNF, NGF and NT sensu stricto) are growth factors that control development, differentiation, synaptic plasticity and survival of several types of neuronal and glial cells in the embryonic and adult central nervous system and sensory organs. Based on the NT role in development and physiology of the nervous system, the present project aims at extending our knowledge on NTs molecular pathways, with emphasis on the their relationships with stress, aging and diseases.
The project will take advantage of as bioinformatic, molecular, genetic, biochemical and behavioural multidisciplinary approaches, with the aim to acquire new insights on the genetic regulatory networks and on the functions exerted by NT and NT receptors during the correct development and in conditions of thermal, social and nutritional stress. A distinctive feature of this research proposal is the use of three different model systems: cells, mouse and zebrafish.
In summary, the main purpose of the present project is to study the molecular, cellular and behavioural phenotype of NTs and NTRs, with emphasis on the relationships of these molecules with stress, ncRNAs and neurodegenerative diseases (NDs).
We are knocking out the BDNF, one of the most known neurotrophin together NGF, in zebrafish using the CRISPR/Cas9 thecnology to he improve our understanding of the role played by NTs during embryonic development and adult brain physiology, with particular attention to the biomedical impact in terms of diagnosis and treatment of neurodegenerative diseases.

What we do

We built a national network, in which the Stazione Zoologica Anton Dohrn of Napoli is the leader Institute, with the aim to merge multidisciplinary approaches and competences to reveal the importance of NT during vertebrate’s brain development.

Partners

Stazione Zoologica Anton Dohrn, Napoli (Unit 1); Dipartimento di Biologia e Biotecnologie "Charles Darwin", Università di Roma Sapienza (Unit 2); Dipartimento di Scienze Biologiche, Università di Napoli Federico II (Unit 3); Laboratorio di Bioinformatica, Università del Sannio (Unit 4).

Research Area

Organismal Biology

Project Lifetime

21 March 2013 to 20 March 2018

SZN Role

Coordinator of the whole project and Research Unit 1

Principal Investigator

Salvatore D’Aniello

Funding Institution

Futuro In Ricerca (FIRB), http://futuroinricerca.miur.it; Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), http://www.istruzione.it        
Grant no. RBFR12QW4I

Contribution to SZN

€369.443 (MIUR contribution)

Publications

D’Agostino Y, Locascio A, Ristoratore F, Sordino P, Spagnuolo A, Borra M* and D’Aniello S* (2015). A rapid and cheap methodology for CRISPR/Cas9 zebrafish mutant screening. Molecular Biotechnology, in press.

Meet the team

Salvatore D’Aniello, Ricercatore
Ylenia D’Agostino, PhD student
Annamaria Locascio, Ricercatore
Filomena Ristoratore, Ricercatore
Paolo Sordino, Ricercatore
Antonietta Spagnuolo, primo Ricercatore

Marie Curie Career Integration Grant (FP7-PEOPLE-2011-CIG)

Summary

The main interest of the project is to study the Nitric Oxide Synthase (NOS) family evolution and its regulation during amphioxus development. In the framework of the project, setting-up an amphioxus facility at the SZN was a priority of national interest, representing the first Italian laboratory working with live amphioxus embryos on demand.
Since Furchgott, Ignarro and Murad won the Nobel Prize in Medicine or Physiology in 1998 for their breakthrough work on the role of nitric oxide (NO) as a multifunctional signaling molecule, many reports have shown the seemingly limitless range of body functions controlled by this compound. To manipulate the endogenous NO level for therapeutic benefits using NOS gene therapy is essential to understand the physiological and developmental functions of different NOS isoforms (nNOS, iNOS, eNOS). Due to their extensive conservation over evolutionary time, one would expect greater differences and structural changes in NOS genes than that we have observed (Andreakis 2011), reflecting the very ancient and essential nature of Nitric Oxide biological pathways.
Surprisingly, a single molecule, identical in all living animals, can fulfil a huge range of different functions. This suggests that differences in the regulation of NOS enzymes expression are key in explaining their functional diversification, functional novelties and degree of complexity.

What we do

We use as animal model system the cephalochordate amphioxus Branchiostoma lanceolatum, from the Gulf of Napoli (Italy) and from Banyuls-sur-Mer (France), with comparative and multidisciplinary approaches in the field of Evolutionary and Developmental Biology (Evo-Devo). The primary aim of this project is to perform a detailed study of the duplicated set of NOS genes during amphioxus development, trying to establish the basic primary NOS roles that are evolutionary conserved in chordates.

Partners

Stazione Zoologica Anton Dohrn, Napoli.

Research Area

Organismal Biology

Project Lifetime

August 2011 to July 2015

SZN Role

Coordinator

Principal Investigator

Salvatore D’Aniello

Funding Institution

European Commission, FP7 Call for Proposal: FP7-PEOPLE-2011-CIG
Grant no. 293871

Contribution to SZN

€100.000 (EU contribution)

Dedicated website

http://cordis.europa.eu/project/rcn/99685_en.html

Publications

Coppola U, Annona G, D’Aniello S* and Ristoratore F* (2015). Rab32/38 duplicated genes in chordate pigmentation: an evolutionary perspective BMC Evolutionary Biology, under review.

Annona G, Holland ND* and D’Aniello S* (2015). Evolution of the notochord. EvoDevo, in press.

Anishchenko E and D’Aniello S* (2015). Tunicate neurogenesis: the case of the SoxB2 missing CNE. Mathematical Models in Biology (Springer), in press.

Vassalli QA, Anishchenko E, Caputi L, Sordino P, D'Aniello S* and Locascio A* (2015). Regulatory elements retained during chordate evolution: Coming across tunicates. Genesis 53: 66-81.

Pascual-Anaya J, D’Aniello S, Kuratani S and Garcia-Fernàndez J (2013). Evolution of the Hox clusters in deuterostomes. BMC Developmental Biology 13: 26.

Meet the team

Salvatore D’Aniello, Ricercatore    
Evgeniya Anishchenko, post-doc
Giovanni Annona, post-doc
Filomena Caccavale, PhD student

Empowering an integrated platform for the study of human diseases with great impact by means of system phenotyping of model animals: mouse and zebrafish clinic (MouZeCLINIC).

Summary

MouZeCLINIC is an infrastructural and training network in biomedicine by means of acquatic and terrestrial model organisms. Through the use of advanced methods of genetic analysis and imaging technologies, MouZeCLINIC aims at performing system phenotyping in zebrafish and mouse models of human diseases. MouZeCLINIC is training a new generation of young researchers by combining the strengths of modern technologies with a real understanding of traditional approaches. The MouZeCLINIC consortium involves two research centers and one academic institution that will provide the MouZeCLINIC fellows with expertise, specialized equipment and training on a wide range of approaches and methodologies incorporated in developmental genetics and translational medicine.

What we do

We are one of the three partners and are contributing by training students, by developing a zebrafish infrastructure and by studying fish models of neuroinflammation, toxicity and metabolism.

Partners

BioGem scarl – Ariano Irpino (Avellino) - IT; Stazione Zoologica Anton Dohrn, Napoli – IT; Università della Magna Graecia – Germaneto (Catanzaro) - IT

Research Area

Organismal Biology

Project Lifetime

January 2012 to July 2015

SZN Role

Partner

Principal Investigator

Paolo Sordino

Funding Institution

Ministero dell’Istruzione dell’Università e della Ricerca (MIUR):
Programma Operativo Nazionale - ”Ricerca e Competitività” 2007-2013
Grant no. PONa3_00239

Contribution to SZN

Infrastructure € 1.273.424,00 (MIUR contribution)
Training € 733.670,00 (MIUR contribution)

Dedicated website

http://www.ponrec.it/open-data/risultati/potenziamento-strutturale/pona3_00239

Publications

Pappalardo A, Porreca I, Caputi L, De Felice E, Schulte-Merker S, Zannini M, Sordino P (in press) Thyroid development in zebrafish lacking TAZ. Mechanisms of Development.

Fortunato AE, Sordino P, Andreakis N (in press) Evolution of the SOUL heme-binding protein superfamily across Eukarya. J Molecular Evolution.

Porreca I, D’Angelo F, Gentilcore D, Carchia E, Amoresano A, Affuso A, Ceccarelli M, De Luca P, Esposito L, Guadagno FM, Mallardo M, Nardone A, Maccarone S, Pane F, Scarfò M, Sordino P, De Felice M, Ambrosino C (2014) Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution. BMC Genomics 15: 1067.

De Felice E, Porreca I, Alleva E, De Girolamo P, Ciriaco E, Germanà A, Sordino P (2014) Localization of BDNF expression in the developing brain of zebrafish. Journal of Anatomy 224: 564.

Ferriero R, Manco G, Lamantea E, Nusco E, Ferrante MI, Sordino P, Stacpoole PW, Lee B, Zeviani M, Brunetti-Pierri N (2013) Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Science Transl Med, 5 (175): 175ra31.

Porreca I, De Felice E, Fagman H, Di Lauro R, Sordino P (2012) Zebrafish bcl2l is a survival factor in thyroid development. Developmental Biology 366:142.

Meet the team

Paolo Sordino, ricercatore