Andreazzoli, M.

Broccoli, V

Di Lauro, C

Gabellini, C

Martini, D

Norton, W

Pucci, C

Sessa, A

Zippo, A

English

Gabellini C

Martini D

Pucci C

Di Lauro C

Norton W

Zippo A

Broccoli V

Sessa A

Andreazzoli M.

Archivio della Ricerca - Università di Pisa

european journal of histochemistrya journal of functional cytologyISSN 1121-760Xvolume 62/ supplement 12018ejhunder the auspices ofthe University of Pavia, Italy64° CONVEGNO GEI SOCIETÀ ITALIANA DI BIOLOGIA DELLOSVILUPPO E DELLA CELLULAL’Aquila, 11-14 June 2018Rettorato GSSI Gran Sasso Science InstituteVia Michele Iacobucci, 2 - 67100 L’AquilaComitato OrganizzatoreAnnamaria CiminiMara MassimiElisabetta BenedettiFrancesco GiansantiMichele d’AngeloVanessa CastelliAndrea AntonosanteMariano CatanesiFederica RagusaComitato ScientificoMario PestarinoFiorenza De BernardiAnnamaria CiminiRodolfo IppolitiFernanda AmicarelliMara MassimiElisabetta BenedettiFrancesco GiansantiSegreteria OrganizzativaDidima Comunicazione SrlsGuest Editors Prof. Mario PestarinoProf.ssa Annamaria Ciminieuropean journal of histochemistrya journal of functional cytologyISSN 1121-760Xvolume 62/ supplement 12018ejhunder the auspices ofthe University of Pavia, ItalyPublished by PAGEPress, Pavia, ItalyEditorial Office:Via A. Cavagna Sangiuliani 5, 27100 Pavia, ItalyPhone: +39.0382.464340 - Fax: +39.0382.34872E-mail: info@pagepress.orgPrinted quarterly by:Press Up s.r.l. via La Spezia, 118/C 00055 - Ladispoli (RM) Phone and Fax: +39.076.15.27.351Annual SubscriptionsEurope: Euro 200All other Countries: $ 250Subscriptions, cancellations, business correspondence andany enquiries must be sent to PAGEPress Publications,Pavia, Italy.Cancellations must be received before the end ofSeptember to take effect at the end of the same year.No part of this publication may be reproduced, stored ina retrieval system or transmitted in any form or by anymeans (electronic, electrostatic, magnetic type, mechani-cal, photocopying or otherwise) without written permis-sion by the Publishers.Reg. Tribunale di Pavia n. 289/23.2.1984.Recognized by the Ministero per i Beni e le AttivitàCulturali, Italy as a publication of high cultural value.                Associato all’USPI Unione Stampa Periodica ItalianaDisclaimer. Whilst every effort is made by the publishersand the editorial board to see that no inaccurate or mislead-ing data, opinion or statement appears in this journal, theywish to make it clear that the data and opinions appearingin the articles or advertisements herein are the responsibil-ity of the contributor or advisor concerned. Accordingly, thepublisher, the editorial board and their respective employ-ees, officers and agents accept no liability whatsoever forthe consequences of any inaccurate or misleading data,opinion or statement.Editor in ChiefC. PellicciariEditorM. BiggiogeraDipartimento di Biologia e Biotecnologie “Lazzaro Spallanzani” Università di PaviaNEURONAL DEVELOPMENT: ORDER AND DISORDERCRISPR/CAS9-INDUCED INACTIVATION OF THE AUTISMRISK GENE SETD5 LEADS TO SOCIAL IMPAIRMENTS INZEBRAFISHC. Gabellini1, D. Martini1, C. Pucci1,2, C. Di Lauro1, W. Norton3, A. Zippo4,5, V. Broccoli6,7, A. Sessa6, M. Andreazzoli11Dep. of Biology, University of Pisa and 2Sant’Anna School ofAdvanced Studies, Pisa, Italy; 3Dep. of Neuroscience, Psychologyand Behaviour, University of Leicester, UK; 4National Ins. ofMolecular Genetics, Milan, Italy; 5Lab. of Chromatin Biology &Epigenetics, Center for Integrative Biology (CIBIO), University ofTrento, Italy; 6Stem Cell and Neurogenesis Unit, Div. ofNeuroscience, San Raffaele Scientific Inst. and 7CNR Inst. ofNeuroscience, Milan, ItalyE-mail: massimiliano.andreazzoli@unipi.itThe SETD5 gene encodes for a putative histone H3 methyltrans-ferase whose loss-of-function (LoF) mutations in humans havebeen recently associated to intellectual disability (ID) and autis-tic spectrum disorders (ASD). The aim of this study is to gener-ate and characterize zebrafish models in which setd5 has beenknocked down or knocked out. setd5 is expressed at early devel-opmental stages while at later stages its expression is localizedto the developing central nervous system (CNS) of zebrafish lar-vae. setd5 morphant embryos are characterized by microcephaly,cardiac edema and reduced locomotor behavior. setd5 knock-down determined a reduction of the expression domain of CNSspecification markers paralleled by a reduced brain size com-pared to control embryos, associated to increased apoptosis.Furthermore, we generated stable setd5 mutant zebrafish linesthrough Crispr/Cas9 strategy: setd5 LoF causes microcephaly, asignificant reduction of body length and locomotor activity.Moreover, we characterized the behaviorial features of heterozy-gous setd5 LoF adults, focusing on social interaction. In partic-ular, in a social preference test, setd5 heterozygous adultsshowed reduced sociality when compared to wild type siblingsand these altered behavioral traits triggered by setd5 LoF areameliorated by risperidone, an antipsychotic drug commonly usedto treat behavioral traits in ASD patients.These zebrafish models will be extremely useful to identify themolecular mechanisms underlying SETD5 LoF phenotype. Thefuture perspective is to screen for targeted compounds able torescue the developmental and behavioral defects, to identifynovel promising therapeutic compounds for individuals affectedby ASD and ID due to SETD5 haploinsufficiency.NEURITIN IN MOUSE NEURONAL DEVELOPMENT: ANEW THERAPEUTIC TARGET FOR RETT SYNDROME? E. Corti, E. Tongiorgi, G. Baj Lab. of Cellular and Developmental Neurobiology, University ofTrieste – Department of Life Sciences, Trieste, ItalyE-mail: gbaj@units.it Rett syndrome (RTT) is a genetic X-linked, progressive neurode-velopmental disorder mainly caused by sporadic mutations in theMECP2 gene. In RTT, neuronal development and synaptic cou-pling are incomplete. In mice, MeCP2 ablation causes neuronaldysfunctions and morphological aberrations, including brainatrophy. The current hypothesis is that neuronal atrophy in RTTis caused by reduced synaptic activity leading to poor trophicsupport of the neuronal dendritic arborization and spines.Among the potential neurotrophic factors candidates to rescueneuronal atrophy, Neuritin has recently emerged for its ability topromote growth and stabilization of axonal and dendritic arbors,synapse formation and maturation during development. Aim ofthis study is to characterize the expression of Neuritin in WT andMeCP2 KO or heterozygous mice brains in order to ascertain apossible disregualtion in the animal model of the pathology andinvestigate its effects on RTT neuronal atrophy. During development, neuronal processes explore their environ-ment to identify appropriate partners before establishing presy-naptic and postsynaptic contacts leading to formation of stablesynapses. We previously showed that this process can be repro-duced in vitro, in primary mouse hippocampal neuronal culturesthat achieve a mature state through 6 developmental stages.Using this in vitro model, we previously identified the develop-mental stages at which neuronal atrophy (days in vitro, DIV, 9-12) and synaptic uncoupling (DIV 15) occur in RTT neurons. Inthis study, we are investigating the expression of Neuritin in WTand KO brains and testing its ability to counteract neuronal atro-phy in MecP2 KO neurons in vitro. Preliminary results show thatlevels of Neuritin in mouse whole brains at post natal day 42 areunchanged while data from primary hippocampal cultures at 12DIV show an mRNA reduction in these neurons. These prelimi-nary results, suggest that Neuritin is disregulated in RTT duringdevelopment but not in the adult brains. DEVELOPMENT OF SEROTONERGIC FIBERS IN THEPOST-NATAL MOUSE BRAINA. Bertero1,2, G. Maddaloni1, M. Pratelli1, N. Barsotti1, A. Boonstra1, A. Giorgi1,2, S. Migliarini1 M. Pasqualetti11Unit of Cell and Developmental Biology, Department of Biology,University of Pisa, Italy; 2Istituto Italiano di Tecnologia, Centerfor Neuroscience and Congnitive Systems, Rovereto (TN), Italy Raphe nuclei serotonergic neurons provide a diffuse innervationof the central nervous system and are involved in the modulationof several functions in both developing and adult brain.1,2Classical studies have described the post-natal development ofserotonergic axons as a linear process of terminal field innerva-tion.3,4 However, technical limitations have hampered a fine mor-phological characterization. We used the Tph2GFP knock-inmouse line, in which GFP expression allows a specific labelling ofserotonergic neurons and axons,5 for confocal microscope imag-ing, and we performed 3-dimensional reconstruction to morpho-logically describe the development of serotonergic fibers in spec-ified brain targets from birth to adulthood. Our analysis high-lighted region-specific developmental patterns of serotonergicfiber density ranging from a linear and progressive colonizationof the target to a transient increase in fiber density occurringwith a region-specific timing. Despite a common pattern of earlypost-natal morphological maturation in which a progressiverearrangement from a dot-shaped to a regular and smooth fibermorphology was observed, starting from post-natal day 28 sero-tonergic fibers acquire the regional morphological featuresobserved in the adult. In conclusion, we provided novel, target-specific insights on the morphology and temporal dynamics ofthe developing serotonergic fibers.1. Jacobs B.L., and Azmitia E.C. Physiol Rev 1992,72(1), 165-229.2. Gaspar P. et al. Nat Rev Neurosci 2003,4(12), 1002-1012. doi:10.1038/nrn1256.3. Levitt P. and Rakic P.  Brain Res 1982,256(1), 35-57.4. Lidov H.G. and Molliver M.E. Brain Res Bull 1982,8(4), 389-430.5. Migliarini S. et al Mol Psychiatry 2013,18(10), 1106-1118. doi:10.1038/mp.2012.128.8Proceedings of the 64th Congress of the Italian Embryological Group (GEI), L’Aquila, 11-14 June 2018

CRISPR/Cas9-induced inactivation of the autism risk gene setd5 leads to social impairments in zebrafish

https://arpi.unipi.it/bitstream/11568/965255/1/2018%20GEI%20L%27Aquila.pdf

CRISPR/Cas9-induced inactivation of the autism risk gene setd5 leads to social impairments in zebrafish

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Archivio della Ricerca - Università di Pisa

Archivio della Ricerca - Università di Pisa