Skip to main content

Iris Salecker

The laboratory will become part of the IBENS in December 2019 and welcomes applications to join the team at all levels.
For additional information about the group, please follow the links to Iris Salecker’s lab website at the Francis Crick Institute, London, UK and her personal lab website.

VISUAL CIRCUIT ASSEMBLY

Background

The brain in all its complexity never ceases to fascinate. It is essential for all aspects of our life, allowing us to interpret sensory information and to generate diverse actions and behaviors. It consists of an immense wealth of neuron subtypes. These are inseparable from another diverse cell population in the brain, the glia. Neuronal and glial processes are organized into intricately patterned circuits, whose correct assembly during development is central for brain function. But how is this achieved? How are different neuron and glial subtypes generated, acquire their distinct identities and morphologies, and eventually come together with astonishing specificity?
To find answers to these questions, our laboratory studies the developing visual system of the fruit fly Drosophila melanogaster. A shared feature of visual circuit architecture is its organization into interconnected columns and layers. While columns are equivalent to an array of channels that receive sensory input from discrete locations across the visual field, layers extract information about specific visual features from each point in space, such as motion or color. Our central aim is to identify the cellular and molecular mechanisms, by which neuron-neuron and neuron-glia interactions shape layered and columnar connectivity in space and time. To do this, our projects use a multidisciplinary strategy, combining molecular biology, genetics, confocal and electron microscopy, transcriptomics and mass spectrometry approaches.
Findings in the fly visual system promise to advance our knowledge of brain development in general. At long term, detailed insights into these mechanisms will serve as foundation to better understand underlying causes of neurodevelopmental and neurodegenerative disorders caused by genetic deficiencies.

Research highlights

The Drosophila retina consists of an almost crystalline array of approximately 750 ommatidia, each containing 8 photoreceptor cells (R1-R8). Their axons extend into the underlying optic lobe, which is subdivided into the lamina, medulla, lobula plate and lobula. All ganglia contain diverse neuron and glial subtypes and share a retinotopic organization into reiterated interconnected columnar minicircuits. The medulla, lobula plate and lobula are additionally structured into perpendicular synaptic layers. The fly visual system is assembled in a series of interdependent steps during larval and pupal stages. By following the coordinated development and interactions of distinct neuron and glial subtypes from birth to branch formation, our laboratory contributed to elucidating key mechanisms that control neuronal and glial formation, specification and circuit wiring.
Our studies rely on tailored genetic strategies to manipulate and visualize specific neuron and glial subtypes with high precision. For instance, inspired by the pioneering Brainbow strategies in mice, we developed the Flybow toolkit as one of the first multicolor cell labeling approaches for Drosophila (Hadjieconomou et al., 2011).
Exploring visual circuit assembly from a neuronal perspective, we uncovered a central role for localized Netrin ligands, provided by intermediate target neurons, in controlling layer-specific targeting of R8 axons that express the Frazzled/Deleted in Colorectal cancer (DCC)/Unc-40 receptor (Timofeev et al., 2012). Investigating the development of motion direction-selective neurons, called T4/T5, we uncovered a novel neurogenesis mode in Drosophila, that involves migratory progenitors and a two-step specification process of neural stem cells. Furthermore, our studies provided insights into the mechanisms that confer layer identity to these neurons at the neuroepithelial level (Apitz and Salecker, 2015, 2016, 2018).
Investigating visual circuit assembly from a glial perspective, we recently established astrocyte-like medulla neuropil glia as a model to study the genetic control of glial branch morphogenesis and identified the Leucine-rich repeat transmembrane protein Lapsyn as a novel determinant controlling this process (Richier, de Miguel Vijandi et al., 2017).
Together, these findings provide the foundation for our current research program at the IBENS.

Link to page/tab Current research interests.

Apitz, H., and Salecker, I. (2018) Spatio-temporal relays control layer identity of direction-selective neuron subtypes in Drosophila. Nature Communications 9, 2295. doi.org/10.1038/s41467-018-04592-z

Richier, B., de Miguel Vijandi, C., Mackenzen, S., and Salecker, I. (2017) Lapsyn controls branch extension and positioning of astrocyte-like glia in the Drosophila optic lobe. Nature Communications 8, 317.
doi.org/10.1038/s41467-017-00384-z

Apitz, H., and Salecker, I. (2016) Retinal determination genes coordinate neuroepithelial specification and neurogenesis modes in the Drosophila optic lobe. Development 143, 2431-2442.
doi.org/10.1242/dev.135004

Apitz, H., and Salecker, I. (2015) A region-specific neurogenesis mode requires migratory progenitors in the Drosophila visual system. Nature Neuroscience 18, 46-55.
doi.org/10.1038/nn.3896

Timofeev, K., Joly, W., Hadjieconomou, D., and Salecker, I. (2012) Localized Netrins act as positional cues to control layer-specific targeting of photoreceptor axons in Drosophila. Neuron 75, 80-93.
doi.org/10.1016/j.neuron.2012.04.037

Hadjieconomou, D., Rotkopf, S., Alexandre, C., Bell, D.M., Dickson, B.J. and Salecker, I. (2011) Flybow: genetic multicolor cell-labeling for neural circuit analysis in Drosophila melanogaster. Nature Methods 8, 260-266.
doi.org/10.1038/nmeth.1567




Adult Drosophilavisual system labeled with Flybow
Adult Drosophilavisual system labeled with Flybow
Layer-specific expression of NetrinB in the pupal optic lobe
Layer-specific expression of NetrinB in the pupal optic lobe
Migratory progenitors in the larval optic lobe
Migratory progenitors in the larval optic lobe
Layered organization of astrocyte branches in the adult visual (...)
Layered organization of astrocyte branches in the adult visual system
Four synaptic layers in the adult lobula plate
Four synaptic layers in the adult lobula plate
Flybow labeled astrocyte branches in the adult medulla.
Flybow labeled astrocyte branches in the adult medulla.
The team's model organism: Drosophila melanogaster
The team’s model organism: Drosophila melanogaster
An eye in an eye
An eye in an eye
Ommatidia in a wild type Drosophilaeye
Ommatidia in a wild type Drosophilaeye