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Overview
We study the developmental programs that lead to the self-assembly of neuronal circuits.
Development produces reproducible patterns of synaptic connectivity. Our goal is to understand how this emerges from dynamical processes that unfold over time and are implemented across multiple interacting levels of biological organization.
Our fundamental premise is that the information giving rise to this outcome is not stored in any single place. It is distributed across gene regulatory networks, molecular players, and cell behaviors, and it is not static. Each developmental moment constrains and enables the next, and the sequence in which events unfold is itself part of the program. In this sense, temporal ordering is not merely descriptive; it is part of the mechanism. Time acts as an organizing variable in the system, not a passive background.
We investigate brain development under this framework, from cell fate specification to the emergence of synaptic connectivity.
We are using single-cell transcriptomics to identify which genes are expressed in each neuron during development. We then combine sophisticated genetic manipulations, live imaging, and behavioral studies to study the mechanisms of neural circuits’ formation during development, and how function and behavior could be compromised when changes in neural wiring arise.
Our science unfolds along the following research axis:
GENE REGULATORY NETWORKS
FROM FATE SPECIFICATION TO NEURONAL DIFERENTIATION
Following neuro-progenitor division, post-mitotic neuronal identity is maintained through the expression of cell-type specific combination of transcription factors, also known as terminal selectors, that define neuro-type specific terminal features. A key gap lies in mechanistically linking the fate specification events during neural progenitor divisions with the establishment of cell-type specific differentiation programs acting in post-mitotic neurons.
To address this problem, we combine multiome profiling (scRNA-seq and scATAC-seq) with advanced genetics and CRISPR-based perturbations to study the differentiation of eight subtypes of motion direction–selective neurons in the Drosophila optic lobe. These neurons originate from two well-characterized progenitor pools (Pinto-Teixeira et al., Cell, 2018), providing a tractable developmental framework to to investigate how fate-specification programs operating in neuroprogenitors install terminal differentiation programs in post-mitotic neurons.
In collaboration with the Özel Lab at Stowers Institute, Kansas City.
Optic lobe of the adult fly. The first visual motion direction sensitive neurons are labeled in green.
DEVELOPMENT OF SUBCELLULAR SYNAPTIC COMPARTMENTALIZATION
The subcellular organization of synaptic connections of different presynaptic neurons into the same output dendrites is a common feature of circuit connectivity, yet the mechanisms underlying this precision remain largely unknown. Elucidating the cellular behaviors and the molecular mechanisms that underlie them is essential for understanding how organized synaptic domains are established during development. We address this problem by investigating the establishment of synaptic connectivity in the dendrites of the T4 visual motion direction-selective neurons in the Drosophila optic lobe.
3D reconstruction of a motion sensing neuron dendrite highlighting its synaptic inputs
POST-TRANSCRIPTIONAL TIMING OF SYNAPTIC PROTEIN EXPRESSION DURING NEURONAL CIRCUIT ASSEMBLY
For a synapse to be functional, the neurotransmitter receptor expressed in the postsynaptic neuron must match the neurotransmitter used by the upstream presynaptic neuron. A central challenge in neuroscience is to understand how synaptic components are timely expressed to match dynamics of circuit assembly. Addressing this problem has been hindered by the lack of systems that allow subcellular resolution in vivo.
We tackle this question by analyzing the temporal dynamics of neurotransmiter receptor protein expression during circuit assembly in the dendrites of T4 motion direction–selective neurons in Drosophila.
In collaboration with the Besse Lab at iBV.
VISUAL NAVIGATION AND NEURONAL PLASTICITY
We investigate the neural substrates of visual motion processing in Drosophila using custom-built virtual reality (VR) setups. We aim to determine how specific variations in synaptic connectivity shape spontaneous behavior and drive long-term behavioral plasticity.
In collaboration with the Wystrach lab at CBI.
Recording behavior of a tethered fly in a virtual reality setup
AND ALSO
IDENTIFICATION OF VISUAL NEURONS INVOLVED IN SOCIAL LEARNING IN DROSOPHILA
Mate-copying occurs when females prefer males that have already attracted other females, a phenomenon observed in many species, including Drosophila and humans.
In this project, led by our collaborator Guillaume Isabel, our specific contribution is to identify the visual neurons involved in mate-copying, and the interneurons linking them to the mushroom body, a central brain structure for memory formation and sensory integration. This contribution will provide critical insights into how visual cues shape social learning, advancing our understanding of the neural mechanisms underlying mate choice.
Drosophila head drawing based on original by Helfrich-Förster.3D dendritic reconstruction done with NeuroNLP.
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