Project description:Signaling pathways control a large number of gene regulatory networks (GRNs) during animal development, acting as major tools for body plan formation. Remarkably, in contrast to the large number of transcription factors present in animal genomes, only a few of these pathways operate during development. Moreover, most of them are largely conserved along metazoan evolution. How evolution has generated a vast diversity of animal morphologies with such a limited number of tools is still largely unknown. Here we show that gain of interconnectivity between signaling pathways, and the GRNs they control, may have played a critical contribution to the origin of vertebrates. We perturbed the retinoic acid, Wnt, FGF and Nodal signaling pathways during gastrulation in amphioxus and zebrafish and comparatively examined its effects in gene expression and cis-regulatory elements (CREs). We found that multiple developmental genes gain response to these pathways through novel CREs in the vertebrate lineage. Moreover, in contrast to amphioxus, many of these CREs are highly interconnected and respond to multiple pathways in zebrafish. Furthermore, we found that vertebrate-specific cell types are more enriched in highly interconnected genes than those tissues with more ancestral origin. Thus, the increase of CREs in vertebrates integrating inputs from different signaling pathways probably contributed to gene expression complexity and the formation of new cell types and morphological novelties in this lineage.
Project description:Signaling pathways control a large number of gene regulatory networks (GRNs) during animal development, acting as major tools for body plan formation. Remarkably, in contrast to the large number of transcription factors present in animal genomes, only a few of these pathways operate during development. Moreover, most of them are largely conserved along metazoan evolution. How evolution has generated a vast diversity of animal morphologies with such a limited number of tools is still largely unknown. Here we show that gain of interconnectivity between signaling pathways, and the GRNs they control, may have played a critical contribution to the origin of vertebrates. We perturbed the retinoic acid, Wnt, FGF and Nodal signaling pathways during gastrulation in amphioxus and zebrafish and comparatively examined its effects in gene expression and cis-regulatory elements (CREs). We found that multiple developmental genes gain response to these pathways through novel CREs in the vertebrate lineage. Moreover, in contrast to amphioxus, many of these CREs are highly interconnected and respond to multiple pathways in zebrafish. Furthermore, we found that vertebrate-specific cell types are more enriched in highly interconnected genes than those tissues with more ancestral origin. Thus, the increase of CREs in vertebrates integrating inputs from different signaling pathways probably contributed to gene expression complexity and the formation of new cell types and morphological novelties in this lineage.
Project description:4C-seq experiments to study the evolution of the chromatin architecture of ancient gene regulatory blocks at the origin of vertebrates.
Project description:The neural crest is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional profiles and chromatin accessibility of neural crest cells in the basal sea lamprey, in order to gain insight into the ancestral state of the neural crest gene regulatory network (GRN) at the dawn of vertebrates. Transcriptome analyses reveal clusters of co-regulated genes during neural crest specification and migration that show high conservation across vertebrates for dynamic programmes like Wnt modulation during the epithelial to mesenchymal transition, but also reveal novel transcription factors and cell-adhesion molecules not previously implicated in neural crest migration. ATAC-seq analysis refines the location of known cis-regulatory elements at the Hox-α2 locus and uncovers novel cis-regulatory elements for Tfap2B and SoxE1. Moreover, cross-species deployment of lamprey elements in zebrafish reveals that the lamprey SoxE1 enhancer activity is deeply conserved, mediating homologous expression in jawed vertebrates. Together, our data provide new insight into the core elements of the GRN that are conserved to the base of the vertebrates, as well as expose elements that are unique to lampreys.
Project description:The hypothalamus coordinates neuroendocrine functions in vertebrates, including circadian rhythm, metabolism, and appetite. To explore its evolutionary origin, we attempt to create integrated transcription/connectome brain maps for swimming tadpoles of the ascidian, Ciona intestinalis, which serves as an approximation of the ancestral proto-vertebrate. This map features several cell types related to different regions of the vertebrate hypothalamus, including coronet cells, magnocellular neurons and the arcuate nucleus. Coronet cells express melanopsin and share additional properties with the saccus vasculosus, a specialized region of the hypothalamus that mediates photoperiodism in non-tropical fishes such as salmon. Comparative transcriptome analyses identified orthologous cell types for mechanosensory switch neurons, and VP+ and VPR+ relay neurons in different regions of the mouse hypothalamus. These observations provide evidence that the hypothalamus predates the evolution of the vertebrate brain. We discuss the possibility that switch neurons, coronet cells, and FoxP+/VPR relay neurons comprise a behavioral circuit that helps trigger metamorphosis of Ciona larvae in response to twilight.