eprintid: 22140 rev_number: 21 eprint_status: archive userid: 2820 dir: disk0/00/02/21/40 datestamp: 2016-11-23 08:47:59 lastmod: 2017-12-05 10:57:25 status_changed: 2016-11-23 08:47:59 type: doctoralThesis metadata_visibility: show creators_name: Martinez Vergara, Hernando title: Descriptive and functional approaches for a system-level understanding of Platynereis dumerilii and the evolution of locomotor circuits in Bilateria subjects: ddc-000 subjects: ddc-004 subjects: ddc-500 subjects: ddc-590 divisions: i-160100 adv_faculty: af-14 abstract: The nervous system, built by the powerful capability of neurons to intercommunicate, is the most fascinating biological achievement, which through evolution has given rise to highly complex structures responsible for remarkable animal behaviours. It is therefore surprising, and at the same time highly motivating for a scientist, to realise how little we know about this evolutionary process. Traditional approaches like palaeontology and phylogenomics lack the resolution to confidently solve the history of neuronal circuits. Nevertheless, thanks to modern comprehensive techniques and integrative approaches, it is possible to molecularly, morphologically and functionally describe entire nervous systems by their constituent components, the cell types. The comparison of cell types and circuits across animals will help elucidate the different evolutionary steps that led to extant nervous systems. Within this thesis, the reader will find a description of the research I have conducted on the implementation of system-level approaches to characterize cell types, with the goal of achieving an integrative understanding of the nervous system of Platynereis dumerilii, an animal suited for these system-level evolutionary studies. A special emphasis has been given to the generation of a new automatic pipeline to build gene expression atlases for complex body plans, the design of image analysis routines to monitor and quantify animal behaviour, and the implementation of the Crispr/Cas9 technique in this organism. I also describe pioneer work to reconstruct the full connectome of the larvae at six days post fertilization, the combination of light-sheet microscopy and calcium indicators to monitor neuronal activity in thousands of neurons, and the proof-of-principle of using optogenetics to manipulate neuronal activity in Platynereis. Because of the relevance of the control of muscle contraction for the evolution of nervous systems, and the vast amount of information collected for various animals with regards to locomotion (Goulding, 2009), I focus my analysis on the post-mitotic Platynereis ventral nerve cord. I show that this structure contains the circuits responsible for the crawling behaviour, and describe in detail the kinematics of these movements, which suggest a similar organization of circuits than vertebrates and segmental protostomes. Using the expression atlas, I unbiasedly unravel the molecular substructure of the ventral nerve cord, which consists of cell types grouped into general medio-lateral domains, remarkably similar to those in vertebrates, as well as different territories unique to protostomes. I further characterize in detail a commissural cell population, showing strong similarities with both vertebrates and Drosophila in terms of position, molecular profile, morphology and function. These findings support the idea of an ancestral cell type, specified by a newly acquired gene, which controlled the coordination between the two sides of the body during locomotion in the bilaterian ancestor. date: 2017 id_scheme: DOI id_number: 10.11588/heidok.00022140 ppn_swb: 1657346587 own_urn: urn:nbn:de:bsz:16-heidok-221409 date_accepted: 2016-10-26 advisor: HASH(0x55fc36c14318) language: eng bibsort: MARTINEZVEDESCRIPTIV2017 full_text_status: public citation: Martinez Vergara, Hernando (2017) Descriptive and functional approaches for a system-level understanding of Platynereis dumerilii and the evolution of locomotor circuits in Bilateria. [Dissertation] document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/22140/1/HernandoMartinez_PhD_thesis_printVersion_reducedSize.pdf