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Faltine-Gonzalez, D. Z.

Publications and source records attributed to Faltine-Gonzalez, D. Z..

5 recordsLinked to original sources

Evolution of new cerebellar nuclei by excitatory progenitor diversification in the early rhombic lip

The cerebellar nuclei, the output regions of the cerebellum, have evolved via repeated duplication of a conserved cell type set to produce different numbers of nuclei across species. Here, we investigate the mechanism underlying this process using developmental single-cell and spatial transcriptomics time courses in mouse and chicken. We show that new nuclei formation is governed by excitatory neurons born from nucleus-specific progenitors in the early and late rhombic lip (RL), with inhibitory neurons incorporating into established nuclear territories. Evolutionarily newer canonical cerebellar nuclei with increasingly higher-order functions are produced by diversification of the early RL, where nuclear identity and spatial organization are established in part by co-option of border formation programs in conserved progenitor cell types. In contrast, the late RL generates the higher-order subnuclei of the medial nucleus and forms a non-canonical olivocerebellar circuit. Together, our findings suggest that new brain regions can evolve through developmental diversification of excitatory progenitors and spatial segregation of conserved sister cell types with generic inhibitory neurons filling in after.

neuroscience↗

BARseq3: a modular system for integrating spatial multi-omics and cellular barcoding in single cells

Understanding cellular identity requires multimodal measurements in single cells. Cellular barcoding provides powerful tools for recording the properties or history of individual cells in nucleic acids, while spatial omics techniques enable the measurement of a growing list of molecular features at micron resolution in tissue. However, existing methods that integrate these approaches in single samples are limited in the modalities they support, their flexibility, and efficiency. Here, we present BARseq3, a modular system that combines cellular barcoding with high-efficiency spatial transcriptomics and translatomics at subcellular resolution in tissue. BARseq3 is compatible with fixed samples, immunostaining, diverse species, and can be easily extended to include other spatial assays, enabling a multimodal understanding of cellular identity.

genomics↗

NvashA function reveals temporal differences in neural subtype generation in cnidarians

Understanding how cnidarians pattern their nervous systems can provide insight into the ancestral mechanisms of neurogenesis that are shared with bilaterians, shedding light on the evolution of nervous systems. While previous studies have revealed deeply conserved mechanisms for neural induction and progenitor selection between cnidarians and bilaterians, less is known about how distinct neuronal subtypes are specified over time in cnidarians. We utilized single-cell mRNA sequencing to profile NvashA-expressing cells across embryonic and planula-larva stages of Nematostella neurogenesis, and functional experiments identified a dynamic role for NvashA over time. Our analysis revealed that unique neuronal subtypes emerge at different developmental stages, providing evidence for temporal patterning in developing cnidarian nerve nets. This can provide a foundation to better our understanding of neurogenic gene regulatory networks, and to compare neurogenesis across cnidarians, and with bilaterians, to improve our knowledge of nervous system evolution.

developmental biology↗

Conserved and lineage-restricted gene regulatory programs modulate developmental cnidocyte specification in Nematostella vectensis.

Cnidocytes are a synapomorphy of cnidarians that have evolved a range of morphologies and functions within and across extant species, which makes them an excellent model to investigate how novel cell types emerge and radiate in evolution. One way to gain insight into how cell types evolve is to investigate the gene regulatory networks (GRNs) that pattern them, leading to the identification of shared and divergent programs that likely represent components of the ancestral and evolved phenotypes. Efforts to identify early acting transcription factors in the sea anemone Nematostella vectensis revealed that NvfoxE-like is a lineage-restricted cnidocyte transcription factor. Expression and functional studies confirmed that NvfoxE-like and its targets are found exclusively in cnidocytes. By investigating interactions with regulators of the known cnidogenesis GRN and comparing the targets of known cnidocyte regulators, we identified at least four regulatory programs contributing to the cnidogenic GRN in Nematostella. The previously identified cnidocyte regulators Nvznf845 and NvpaxA represent two core pan-cnidarian regulatory programs, while the NvfoxE-like dependent program appears to be restricted to Hexacorallia or Actinaria, where we hypothesize it functions to pattern the unique capsule features present in those lineages. Here, we confirm the hypothesized core conserved transcriptional program, as well as demonstrate how a novel transcription factor was co-opted into cnidogenesis in a subset of cnidarians, thus contributing to the diversification and continued evolution of cnidocytes.

evolutionary biology↗

Brain regulatory program predates central nervous system evolution

Understanding if bilaterian centralized nervous systems (CNS) evolved once or multiple times has been debated for over a century. Recent efforts determined that the nerve chords found in bilaterian CNSs likely evolved independently, but the origin(s) of brains remains debatable. Developing brains are regionalized by stripes of gene expression along the anteroposterior axis. Gene homologs are expressed in the same relative order in disparate species, which has been interpreted as evidence for homology. However, regionalization programs resemble anteroposterior axial patterning programs, which supports an alternative model by which conserved expression in brains arose convergently through the independent co-option of deeply conserved axial patterning programs. To begin resolving these hypotheses, we sought to determine when the neurogenic role for axial programs evolved. Here we show that the nerve net in the cnidarian Nematostella vectensis and bilaterian brain are regionalized by the same molecular programs, which indicates nervous system regionalization predates the emergence of bilaterians and CNSs altogether. This argues that shared regionalization mechanisms are insufficient to support the homology of brains and supports the notion that axial programs were able to be co-opted multiple times during evolution of brains.

evolutionary biology↗