For the nervous system to function properly, each neuron must be made in the right place at the right time during development. Once neurons are formed, they often embark on long journeys to their final destination. When this precise spatial and temporal program is perturbed, cancer, degeneration or other neurologic diseases may result. Researchers in DNB are advancing our understanding of these highly dynamic processes with unprecedented resolution. How are different cell types produced? How do defects in spatial and temporal coordination during embryogenesis impact function? When do cells signal to each other to coordinate their developmental programs? Can these developmental programs be altered to drive evolutionary adaptation? Fundamental developmental biology is the foundation for most of our research in DNB.
Understanding the molecular detail underlying basic mechanisms of organelle quality control and organelle trafficking in neurons.
Research highlights
Discovery of ‘pliancy genes’ showcases role of latent epigenetic programs in retinal recovery
Using single-cell RNA seq and ATAC-seq researchers identified cell-type-specific changes in chromatin structure during development. They uncovered several hundred genes that are transcriptionally ‘silent’ but which still had accessible chromatin - most of these genes were found in Müller Glia. The researchers showed that these genes are enriched in pathways related to inflammation, angiogenesis and other types of cell signaling. These ‘pliancy genes’ allow the Müller Glia to rapidly change their gene expression and cellular state.
YAP/TAZ maintain the proliferative capacity and structural organization of radial glial cells during brain development
It has been established that aberrant YAP/TAZ activation is detrimental to mammalian brain development, but whether and how endogenous levels of YAP/TAZ activity regulate brain development remain unclear. Work led by Xinwei Cao, PhD uncovered essential functions of YAP/TAZ during mammalian brain development, revealing the transcriptional mechanism of action.
Identification of a modular super-enhancer in murine retinal development
In the developing retina, Vsx2 is expressed in retinal progenitor cells and is maintained in differentiated bipolar neurons and Müller glia. A single super-enhancer controls this complex and dynamic pattern of expression. Findings from the Dyer lab reveal that this prototypical super-enhancer may serve as a model for dissecting the complex gene expression patterns for neurogenic transcription factors during development.
