article published yes Johann W. Markovitsch author Daniel Mitić author Alisa Del Pilar Jiménez García author Alsberga Zane author 60f7509a-f652-11ea-9d86-b963d6490d7c0009-0003-0415-7603 Sarah Kainz author Rashmit Kaur author Thomas Hummel author MiSi department GradSch department Structural and functional differences between brain hemispheres are a common feature of animal nervous systems with reduced bilateral asymmetry often linked to impaired cognitive performance. How neuronal left-right asymmetry is initiated and integrated into a bilaterally symmetrical ground pattern is poorly understood. Here, we show that the directional asymmetry of a Drosophila central brain circuit originates from axonal interactions of two types of bilateral pioneer neurons. Subsequent recruitment of neighboring neurons into the asymmetric neuropil primordium results in hemisphere-specific microcircuits. Circuit lateralization requires dynamic expression of the cell adhesion molecule Fasciclin 2 to maintain structural plasticity in axonal remodeling. Reduced circuit asymmetry following cell type–specific Fasciclin 2 manipulation affects adult brain function. These results reveal an unexpected degree of developmental plasticity of late-born Drosophila neurons in the formation of a circuit node via the lateralized recruitment of symmetric circuit components. https://research-explorer.ista.ac.at/download/21707/21786/2026_ScienceAdv_Markovitsch.pdf application/pdfno American Association for the Advancement of Science2026 eng 2375-254810.1126/sciadv.aea6020 1213 Markovitsch JW, Mitić D, Del Pilar Jiménez García A, Zane A, Kainz S, Kaur R, Hummel T. 2026. Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity. Science Advances. 12(13), eaea6020. Markovitsch, Johann W., et al. “Sequential Formation of Drosophila Circuit Asymmetry via Prolonged Structural Plasticity.” <i>Science Advances</i>, vol. 12, no. 13, eaea6020, American Association for the Advancement of Science, 2026, doi:<a href="https://doi.org/10.1126/sciadv.aea6020">10.1126/sciadv.aea6020</a>. J.W. Markovitsch, D. Mitić, A. Del Pilar Jiménez García, A. Zane, S. Kainz, R. Kaur, T. Hummel, Science Advances 12 (2026). Markovitsch, Johann W., Daniel Mitić, Alisa Del Pilar Jiménez García, Alsberga Zane, Sarah Kainz, Rashmit Kaur, and Thomas Hummel. “Sequential Formation of Drosophila Circuit Asymmetry via Prolonged Structural Plasticity.” <i>Science Advances</i>. American Association for the Advancement of Science, 2026. <a href="https://doi.org/10.1126/sciadv.aea6020">https://doi.org/10.1126/sciadv.aea6020</a>. J. W. Markovitsch <i>et al.</i>, “Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity,” <i>Science Advances</i>, vol. 12, no. 13. American Association for the Advancement of Science, 2026. Markovitsch, J. W., Mitić, D., Del Pilar Jiménez García, A., Zane, A., Kainz, S., Kaur, R., &#38; Hummel, T. (2026). Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity. <i>Science Advances</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.aea6020">https://doi.org/10.1126/sciadv.aea6020</a> Markovitsch JW, Mitić D, Del Pilar Jiménez García A, et al. Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity. <i>Science Advances</i>. 2026;12(13). doi:<a href="https://doi.org/10.1126/sciadv.aea6020">10.1126/sciadv.aea6020</a> 217072026-04-12T22:01:48Z2026-05-04T09:18:06Z