Dombrovski Lab
Molecular Principles of Brain Wiring:
from genes to behaviors
from genes to behaviors
Welcome to the Dombrovski Lab at the University of Colorado Boulder!
Our lab studies how the brain builds precise wiring. In every brain, from insects to humans, each neuron must form the right connections at the right time. In a human brain, this means hundreds of billions of neurons assembling into circuits through trillions of specific synaptic choices — a level of precision that remains far beyond what we can fully analyze or experimentally control.
© Sanes and Zipursky, 2020.
© FlyWire Consortium (Dorkenwald et al.) —
Whole-brain EM connectome of Drosophila melanogaster.
Whole-brain EM connectome of Drosophila melanogaster.
© Getty Images — Yuichiro Chino
Fly brain - 10 neurons, 2 x 10 synapses
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Human brain - 10 neurons, 10 synapses
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To understand the fundamental rules behind this wiring, we work with a powerful model: the Drosophila (fruit fly) brain. It hasabout 100,000 neurons and a fully mapped synaptic connectome, along with comprehensive developmental single-cell transcriptomes and virtually unlimited genetic tools. This unique combination lets us link neural structure, gene expression, and circuit function with a level of resolution thatis not yet possible in larger brains.
A core idea in the field is that neurons achieve this precision through synaptic specificity — the ability of each neuron to recognize the correct partners among many possible targets. This recognition is controlled by a diverse set of cell-surface «wiring molecules», or neuronal recognition proteins, that act as a molecular code for partner matching. Yet how individual neurons select, regulate, and deploy these molecules, so that the developing fly brain assembles ~ 20 million precise synapses, remains unknown.
We aim to uncover this molecular logic.
We combine genetics, anatomy, single-cell genomics, and spatial transcriptomics to decode the expression, localization, and function of wiring molecules, and to identify the transcriptional programs that guide cell-type identity, recognition, and synaptic specificity in the developing brain. Our goal is to build predictive models of how neurons connect and to reveal the basic rules that any brain uses to form its circuits.
We combine genetics, anatomy, single-cell genomics, and spatial transcriptomics to decode the expression, localization, and function of wiring molecules, and to identify the transcriptional programs that guide cell-type identity, recognition, and synaptic specificity in the developing brain. Our goal is to build predictive models of how neurons connect and to reveal the basic rules that any brain uses to form its circuits.
