I am very happy (and a bit scared) to present to you what we have been working on over the last 4 years. This manuscript is exactly what I dreamt of when I started the lab and I could not be happier and prouder of the outcome!
Evolutionary dynamics of temporal transcription factor series in the insect optic lobe
biorxiv.org/content/10.64898/20…
You can find the paper here and, if you are interested, read the thread below
www.biorxiv.org/content/10.6...
Evolutionary dynamics of temporal transcription factor series in the insect optic lobe
The nervous system is composed of a wide diversity of neuronal cell types arranged into complex circuits that support a broad range of behaviors. Patterning of neural stem cells in time through the ex...
While I was a post-doc with Claude Desplan, I studied how neuronal types are specified in the Drosophila visual brain through a process called temporal patterning, which is the successive expression of temporal transcription factors in neuroblasts that change their ability to generate cell types.
This is a widespread phenomenon in nervous systems, however the "actors" (the temporal transcription factors - tTFs) differ. We asked "how did these temporal programs evolve?". Konstantina Filippopoulou collected eight different insect species that span almost the entire insect phylogenetic tree.
She performed single-cell mRNA sequencing in their developing optic lobes and used trajectory inference to predict their tTFs. What we saw was pretty stunning: the insect ancestor of hemi- and holo-metabolous insects 400 million years ago already had a very complex series.
Konstantina didn't only rely on the sequencing data; she performed more than 100 HCR-FISH experiments to confirm the in silico analysis, but also to visualise them in situ in 8 different developing insect visual brains!
Of course, insects have conquered the world and adapted in very different environments; their nervous system has to change. Indeed, we found a number of species-specific modifications and we reconstructed the evolutionary history of the temporal series in these insects.
We grouped these events in four distinct categories: what I find quite remarkable is that each of these mechanisms can be expected to affect neuronal diversity to a different extent.
It could change neuronal identity fundamentally (e.g. the absence of a temporal window or the introduction of a new tTF from a different developmental context) or to a smaller extent (e.g. the substitution of a Sox TF by another Sox TF or the gain of a new tTF in an existing temporal window)
Come to think about it, this graded spectrum of effects could provide evolution with a flexible means to modulate neuronal diversity without destabilizing developmental programs. Personally, I find this hypothesis super-interesting!
Of course, these changes in temporal programs are not only "cosmetic". They translate directly into changes in neuronal identity. We looked in a bit more detail in the effects of these different changes in Musca and saw differences in neuronal type diversity.
We believe that our results reveal both a deep conservation of developmental logic, as well as a remarkable evolutionary plasticity and they establish the temporal transcription factor series as a powerful, tractable substrate for the evolution of neuronal diversity.
This work didn't happen in a vacuum and benefited by wonderful collaborators in our lab, namely Elsa Iliopoulou and Claire Julliot de La Morandière, as well as the labs of
@jsb-ucla.bsky.social and
@tonigabaldon.bsky.social.
Jan 10, 2026 09:42Here, I really want to highlight Konstantina's huge work that involved rearing and establishing protocols for 8(!) different insects in our lab (which when she joined was a collection of empty benches) - a massive achievement. I was extremely lucky to have her as my first recruitment in the lab.
I would love to thank everyone that believed in this project and, in particular, the
@ijmonod.bsky.social that provided an ideal, supportive environment for this work, and the
@erc.europa.eu that funded this work.
I would also like to thank the ones that didn't believe in this work either - they gave us some extra motivation to prove them wrong :-)