Uncovering the Molecular Basis of Brain Connections
The Chen Lab studies how neurons form precise connections during development, enabling organisms to sense and respond to the world around them.
Our Mission
We use precise genetic tools to reveal the principles of neural wiring
The Chen Lab studies how neurons form precise connections during development, using the fruit fly (Drosophila melanogaster) as a model system. A central part of our approach is building genetic tools such as split-GAL4 lines that let us label and control individual neuron types at specific stages of development. Alongside our research, we are committed to training the next generation of neurobiologists and contributing to the broader developmental neuroscience community.
Wiring the Visual Brain: Finding the Right Target
How does a developing neuron know exactly where in the brain to send its branches? We study a single developing visual neuron that reaches into four different brain regions, using it to uncover the genetic instructions that guide each connection to its correct destination.
Keeping the Picture Straight: Precision in Visual Mapping
Our eyes and brains are wired together like a perfectly aligned grid: every point in the eye maps to a matching point in the brain. We're studying how this precise map is built during development, and what happens when that precision breaks down.
How Chance Becomes Order: Wiring a Randomized Circuit
Some neurons "choose" their identity at random, yet the circuits they build are remarkably precise and reproducible. We're tracing how this random decision is communicated to downstream partners to construct a reliable, functioning circuit.
Lab News & Updates
Our Unique Approach
We Create Precise Genetic Tools to Target Specific Neuron Types
How do we identify and manipulate specific cell types in the brain to study their function? Our lab addresses this challenge by creating precise genetic tools that target specific neuron types across all developmental stages in Drosophila.
Our approach uses single-cell RNA sequencing (scRNA-seq) data to develop gene-specific split-GAL4 lines. Unlike traditional enhancer-based tools, which often lack specificity and can fail to work consistently across development, our method targets regulatory elements identified directly from scRNA-seq data — resulting in highly predictive, reliable tools for targeted genetic manipulation.
During my postdoc, I led a team of undergraduates to streamline the protocol for generating split-GAL4 lines (Li & Li et al., 2023, STAR Protocols). Using this protocol, approximately 3,000 existing fly lines from the Drosophila Stock Center can be converted into split-GAL4 lines, enabling precise targeting of cell types across diverse tissues. Our lab actively collaborates with researchers at Columbia, UPenn, and the University of Toulouse to expand this toolkit and apply it to developmental and functional studies across Drosophila neurobiology.
Recent Project Highlight
Uncovering the Molecular Controls of Neuropil Targeting in Developing Sensory Circuits
How do developing neurons know where to extend their branches in the brain? Understanding how immature neurons develop specific structures that allow them to connect with precise brain regions is a key question in our lab. We are using the TmY14 neuron in the Drosophila visual system to tackle this challenge. TmY14 neurons extend branches to multiple regions — the medulla, lobula, lobula plate, and the central brain. We have identified three transcription factors that specifically regulate projections to the lobula. Our ongoing work focuses on unraveling the molecular network involving these transcription factors and identifying the downstream signals that direct neuronal targeting and circuit formation.
Join Our Lab!
The Chen Lab is a collaborative group passionate about neurobiology and genetics. We strive to build a respectful, inclusive, and exciting environment where students can grow and contribute to our collective knowledge. Meet our team and learn about upcoming opportunities to get involved!