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.
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:The hypothalamus is one of the most complex brain structures whose development involves a plastic process of neuronal fate specification. Progress has been made to decipher the gene regulatory programs that are responsible for hypothalamus development; however, the molecular developmetal trajectory of hyothalamus is largely unknown. To understand how pre- and postmitotic transcriptional programs interact and coordinate to endow neuronal cell subtypes with their characteristic properties during hypothalamic development, we performed single-cell RNA sequencing (scRNA-seq) on single cells derived from Rax+ hypothalamic neuroepithelium at four critical developmental points during hypothalamic development. Our single-cell analysis provides a developmental landscape of mouse hypothalamus. We show that while the fate of radial glial cells (RGCs) is predetermined before differentiation but lack spatial code to distinguish from each other, different clusters of intermediate progenitors (IPCs) emerge to display diversifying fates and subdivide hypothalamic primordium into distinct spatially-restricted progenitor domains. We further characterize the maturation dynamics of hypothalamic neurons and suggest that immature neurons could evolve into multiple peptidergic neuronal subtypes. Finally, we identify sets of transcription factors (TFs) serving as regulons to determine the fate of diverse GABAergic and Glutamatergic neurons in hypothalamus. Together, our study offers a single-cell transcriptional framework for the hypothalamus developmental trajectory and propose a cascade diversifying model to deconstruct the origin of neuronal diversity in hypothalamus.
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:he neural crest is an embryonic stem cell population unique to vertebrates whose expansion and diversification are thought to have promoted vertebrate evolution by enabling emergence of novel cell types and structures like jaws and peripheral ganglia2. While basal vertebrates have sensory ganglia, convention has it that trunk sympathetic chain ganglia arose only in jawed vertebrates. In contrast, here we report the presence of trunk sympathetic neurons in the sea lamprey, Petromyzon marinus, an extant jawless vertebrate. These neurons arise from sympathoblasts near the dorsal aorta that undergo noradrenergic specification via a transcriptional program homologous to that described in gnathostomes. Lamprey sympathoblasts populate the extracardiac space and extend along the length of the trunk in bilateral streams, expressing the catecholamine biosynthetic pathway enzymes tyrosine hydroxylase and dopamine -hydroxylase. CM-DiI lineage tracing analysis further confirmed that these cells derive from the trunk neural crest. RNA-seq of isolated ammocete trunk sympathoblasts revealed gene profiles characteristic of sympathetic neuron function. Our findings challenge prevailing dogma which posits that sympathetic ganglia are a gnathostome innovation, instead suggesting that a late-developing rudimentary sympathetic nervous system may have been characteristic of the earliest vertebrates.