Robert J. Johnston, Jr. PhD

Assistant Professor of Biology

robertjohnston@jhu.edu
Telephone Number: 410-516-4954

Johns Hopkins University
3400 N. Charles St.
Baltimore, MD 21218
Room: Mudd Hall 309
Areas of Research
Cellular + Molecular Neuroscience
Developmental Neuroscience

Graduate Program Affiliations

Neuroscience Training Program

Cellular, Molecular, Developmental and Biophysics (CMDB) Graduate Program

Generating neuronal diversity in fly eyes and human retinal organoids

A central challenge in developmental neurobiology is to understand how the incredible diversity of neuronal cell types is generated. My lab studies this question in the color vision systems of flies and humans. By studying highly divergent organisms, we aim to identify fundamental mechanisms that diversify neuronal function during development.

Our studies in flies address the mechanisms controlling stochastic photoreceptor patterning during development and the role of nuclear architecture in gene regulation. Two subtypes of color-detecting photoreceptors are randomly patterned across the fly retina. We found that a mechanism involving transcriptional priming, chromatin compaction, and enhancer accessibility determines stochastic expression of a transcription factor that controls patterning in the retina. This mechanism may represent a general paradigm for gene regulation during development. Our studies of nuclear architecture focus on the pairing of homologous chromosomes in somatic cells, which enables gene regulation between chromosomes. We found that clusters of DNA-looping insulators and chromatin structures called topologically associating domains (TADs) act to button chromosomes together to promote interchromosomal gene regulation. Our findings highlight how distinct elements in the genome drive physical interactions between chromosomes to regulate gene expression.

In humans, three subtypes of cone photoreceptors enable trichromatic color and high acuity vision. To overcome the challenges associated with studies of human development, we utilized a human organoid system that recapitulates retinal development and photoreceptor specification. We found that spatiotemporal regulation of thyroid hormone and retinoic acid signaling specifies cone subtypes in human retinal organoids. Our studies advanced human retinal organoids as a model for revealing mechanisms of human development, with promising utility for therapeutics and vision repair.


 

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