eprintid: 34420 rev_number: 12 eprint_status: archive userid: 7615 dir: disk0/00/03/44/20 datestamp: 2024-02-08 14:05:53 lastmod: 2024-02-14 13:07:43 status_changed: 2024-02-08 14:05:53 type: doctoralThesis metadata_visibility: show creators_name: Hervas Sotomayor, Francisca title: Tracing the origins and evolution of the vertebrate brain: a comparative cellular study in anamniotes subjects: ddc-570 divisions: i-140001 adv_faculty: af-14 abstract: Vertebrates, a diverse group of organisms adapted to a range of ecological niches, rely on external cues for responding to environmental pressures. The brain plays a crucial role in processing this information and coordinating the corresponding responses. Despite this adaptation diversity, the fundamental patterning of this organ into prosencephalon, mesencephalon, and rhombencephalon appears to be conserved across all extant vertebrate species, suggesting an ancestral organization. Although scientists have studied the brain comparatively to understand its origin and evolution, most research has focused on amniotes. This narrow focus, however, has hampered a clear understanding of the origin of multiple structures that predate this lineage. In this thesis, I address this gap by comparatively analyzing the cell composition of the brains of multiple non-amniotes. My goal was to better understand the cellular and molecular origins of this organ and its diversification through evolution. To accomplish that, the first step involved generating a comprehensive and spatially resolved transcriptomic cell type atlas for the brain of the sea lamprey, a cyclostome whose phylogenetic position allows for the inference of ancestral vertebrate traits. This endeavor was complemented by producing and integrating data for catshark, spotted gar, and lungfish; species that belong to main gnathostome lineages, enabling trait reconstruction within the vertebrate clade. By comparing broad cell classes between these species, I discovered conserved expression profiles of transcription factors and effector genes, indicating that these classes are homologous across vertebrates. The comparative analysis between mice and lamprey atlases further discerned shared cell type families. Additionally, the identification of the main embryonic sources of telencephalic inhibitory neurons in the lamprey brain, confirmed their existence in vertebrate ancestors. The analyses also revealed key tissues and cell types that probably emerged later in evolution, after the divergence of cyclostomes and gnathostomes. For instance, the ancestral brain probably lacked cerebellar cells and oligodendrocytes (myelinating cells); the latter likely evolved in gnathostomes from an astrocyte-like cell. It seems that the ancestral glia already possessed certain elements of the molecular machinery involved in oligodendrocyte differentiation and myelin production. However, crucial genes from this machinery appeared only in gnathostomes. This indicates that the genome duplication, which occurred in this group, played a role in the emergence of these cell types. Furthermore, it's likely that the vertebrate ancestor had a single-domain pallium homologous to the multiple-domain pallium present in tetrapods. The analyses between gnathostomes suggested that while there is a clear indication of homology among the pallial neurons at a broad scale, the existence of one-to-one homologies remains questionable. Collectively, my research identifies the ancestral cellular configuration and molecular core of the vertebrate brain. Additionally, I provide insights into the cellular diversification that has accompanied the evolution of the clade. Notably, these findings not only address unresolved questions in comparative neuroscience but also point to new directions concerning the temporal and mechanistic dynamics behind the evolution of tissues, such as the pallium, amygdala and cerebellum. Finally, by focusing on anamniotes, these results contribute substantially to the refinement of brain evolution models in vertebrates. date: 2024 id_scheme: DOI id_number: 10.11588/heidok.00034420 ppn_swb: 1880751771 own_urn: urn:nbn:de:bsz:16-heidok-344207 date_accepted: 2024-02-02 advisor: HASH(0x55e83b01ff88) language: eng bibsort: HERVASSOTOTRACINGTHE20240207 full_text_status: public place_of_pub: Heidelberg citation: Hervas Sotomayor, Francisca (2024) Tracing the origins and evolution of the vertebrate brain: a comparative cellular study in anamniotes. [Dissertation] document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34420/1/Francisca_Hervas_Sotomayor_thesis.pdf