Shared neurogenesis onset is sufficient to explain bilateral matching in the vertebrate retina

Bilateral symmetry is a hallmark of many paired organs and often essential for optimal functionality. The vertebrate eyes are a prominent example of this, as the matched development of the two retinas is required for accurate visual processing.

While macroscopic aspects of symmetry emergence across systems have been investigated, how bilateral matching is maintained once cells start to differentiate remains less understood. Here we address this question using the zebrafish retina as a model to follow neurogenic programs in vivo at single-cell resolution. We perform quantitative 3D live imaging of both retinas simultaneously and directly compare neurogenesis onset and propagation within and across embryos. We find that neurogenic waves initiate at the retinal poles and progress towards the mid-retina in a conserved spatiotemporal pattern. Within embryos, the two eyes exhibit highly similar neurogenesis dynamics when it comes to timing of neurogenesis onset, cell number increase, and spatial wave progression. Across embryos, however, variability is larger. While these observations hint at active inter-retinal coordination, a stochastic model predicts that a shared onset of neurogenesis can be sufficient to explain bilateral matching. Targeted genetic perturbation experiments support this prediction. We find that altering wave propagation affects patterning but not bilateral similarity. Disrupting neurogenesis onset timing, however, reduces bilateral symmetry between eyes.

Thus, the combination of experiment and theory identifies synchronized neurogenesis onset as a key determinant of bilateral symmetry, revealing a minimal principle for how reproducible development of paired organs can emerge from stochastic processes.