Publications by authors named "M Robert Wirthlin"
We present an enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct and indirect pathway MSNs, as well as Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes of virus delivery, and with diverse transgene cargos.
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- The mammalian cortex consists of different cell types that have specific properties, which are important for understanding how the cortex functions in both health and disease.
- Researchers utilized data from mouse and human studies to identify marker genes and enhancers for various cortical cell types, creating a comprehensive set of tools for targeting these cells specifically.
- They introduced fifteen new transgenic driver lines, two new reporter lines, and over 800 enhancer AAVs, facilitating a wide range of experimental approaches to study the mammalian cortex and its functions.
Article Synopsis
- The study investigates the genetic and brain features linked to vocal learning in mammals by comparing data from the Egyptian fruit bat and 215 other placental mammals.* -
- Researchers found that certain proteins evolve more slowly in vocal learners and identified a specific brain region responsible for vocal motor control in the Egyptian fruit bat.* -
- Using machine learning, they uncovered 50 regulatory elements that are associated with vocal learning, suggesting that losses in these elements played a role in the evolution of vocal learning in mammals.*
Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations between enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent and functionally conserved despite low sequence conservation. We developed the Tissue-Aware Conservation Inference Toolkit (TACIT) to associate candidate enhancers with species' phenotypes using predictions from machine learning models trained on specific tissues.
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- Zoonomia is the largest resource for studying mammalian genomes, analyzing 240 species to find genetic mutations that could impact fitness and disease risk.
- Around 332 million bases in the human genome are highly conserved across species, indicating evolutionary significance, with 4552 of these being ultraconserved.
- The research highlights that most constrained bases are outside protein-coding regions and not annotated, revealing potential insights for understanding unique traits in mammals and informing medical research.