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Trevers, K. E.

Publications and source records attributed to Trevers, K. E..

3 recordsLinked to original sources

Lateralized Tenm4 expression biases visual performance and modulates axonal growth and pre-synapse size in retinal ganglion cells

The precise wiring of neuronal connections is a striking feature of the central nervous system and is critical for correct brain function. During vertebrate visual development, retinal ganglion cells (RGCs) establish synaptic connections with postsynaptic cells in the optic tectum, a process that is in part conferred by cell adhesion molecules. However, a complete understanding of the retinotectal wiring mechanism is lacking. Here, we show that the synaptic adhesion molecule Teneurin-4 (Tenm4) is expressed by RGCs and their postsynaptic tectal cell targets in a left-right side-specific manner in zebrafish. Loss of tenm4 leads to defects in presynaptic structures in RGCs and further affects their axonal growth and arbor complexity. Functional assessment of RGC responses to visual stimuli showed a general increase in response amplitude in mutant animals. Visual behavioral analysis revealed a deficit with a strong left-right asymmetrical component in mutant larvae. Our findings demonstrate that tenm4 plays an important role in sensorimotor circuit assembly, extending to neural activities and visual acuity.

neuroscience↗

The organizer as a cooperative of signaling cells for neural induction

The "organizer", discovered 100 years ago by Hans Spemann and Hilde Mangold, is a special region of vertebrate embryos at the gastrula stage; it emits signals that can re-direct the fate of neighboring cells to acquire neural plate identity. It is generally imagined as unique population of cells producing one or a few signaling molecules, responsible for neural induction and for patterning the neural plate and the mesoderm. Here we use single cell and tissue transcriptomics to explore the expression of signaling molecules in the node (the amniote organizer). Although all organizer cells express the homeobox gene Goosecoid, node cells show a diversity of transcription factor signatures associated with expression of subsets of many signaling molecules, suggesting distinct cell sub-populations. Using a recently described Gene Regulatory Network (GRN) of 175 transcriptional responses to neural induction, we explore the activities of 22 of these signals and find that some of them regulate the expression of components of the GRN that are not responsive to previously described pathways associated with neural induction. These results suggest that rather than a single, static, homogeneous population, the organizer comprises a diverse collective of specialized cells that emit cooperating signals to instruct receiving neighbors to adopt their new identities. Significance StatementThe Spemann-Mangold organizer is an embryonic region that can induce the formation of a fully patterned nervous system from non-neural embryonic cells. Here we show that it is made up of a diversity of cell populations that emit distinct sets of signals, which cooperate to account for the repertoire of molecular responses in receiving cells. Several of these signals had not previously been associated with neural induction or patterning.

developmental biology↗

A gene regulatory network for neural induction

During early vertebrate development, signals from a special region of the embryo, the organizer, can re-direct the fate of non-neural ectoderm cells to form a complete, patterned nervous system. This is called neural induction and has generally been imagined as a single signalling event, causing a switch of fate. Here we undertake a comprehensive analysis, in very fine time-course, of the events following exposure of ectoderm to the organizer. Using transcriptomics and epigenomics we generate a Gene Regulatory Network comprising 175 transcriptional regulators and 5,614 predicted interactions between them, with fine temporal dynamics from initial exposure to the signals to expression of mature neural plate markers. Using in situ hybridization, single-cell RNA-sequencing and reporter assays we show that neural induction by a grafted organizer closely resembles normal neural plate development. The study is accompanied by a comprehensive resource including information about conservation of the predicted enhancers in different vertebrate systems.

developmental biology↗