skip to Main Content

JNK signaling in pioneer neurons organizes ventral nerve cord architecture in Drosophila embryos


Morphogenesis of the Central Nervous System (CNS) is a complex process that obeys precise architectural rules. Yet, the mechanisms dictating these rules remain unknown. Analyzing morphogenesis of the Drosophila embryo Ventral Nerve Cord (VNC), we observe that a tight control of JNK signaling is essential for attaining the final VNC architecture. JNK signaling in a specific subset of pioneer neurons autonomously regulates the expression of Fasciclin 2 (Fas 2) and Neurexin IV (Nrx IV) adhesion molecules, probably via the transcription factor zfh1. Interfering at any step in this cascade affects fasciculation along pioneer axons, leading to secondary cumulative scaffolding defects during the structural organization of the axonal network. The global disorder of architectural landmarks ultimately influences nervous system condensation. In summary, our data point to JNK signaling in a subset of pioneer neurons as a key element underpinning VNC architecture, revealing critical milestones on the mechanism of control of its structural organization.


Karkali, K., Saunders, T.E., Panayotou, G., Martin-Blanco, E. JNK signaling in pioneer neurons organizes ventral nerve cord architecture in Drosophila embryos. Nat Commun 14, 675 (2023).

a Regulatory network modulating VNC architectural organization and condensation. Precise JNK activity levels in early-specified neurons (aCC, pCC, RP2 and VUMs) are regulated by a primary negative feedback loop mediated by Puc. Excessive JNK activity in puc mutants or upon early overexpression of HepCA (constitutively active JNKK) in aCC, pCC, RP2 and/or VUMs neurons leads to a general downregulation of Fas 2 (mainly autonomous) and an increase in Nrx IV expression. This affects the general architectural robustness of the VNC, preventing its condensation. Zfh1 acts as an intermediate factor in pioneers regulating Fas 2 and Nrx IV expression in response to JNK activity. On the other hand, Zfh1, negatively, and Fas 2, positively, affect JNK activity, establishing secondary control loops. Regulatory links at the level of expression control are indicated by continuous lines (Dark Green - positive; Dark Red- negative). Links at the level of activity control are represented by discontinuous lines (Light Green - positive; Light Red - negative). Schematic diagrams of the aCC, pCC, RP2 and VUM neurons are color coded as in (b). b The modification of the canonical topography and axonal paths of pioneer neurons by alterations in JNK activity levels disturbs their instructive structural roles. The RN2 positive longitudinal connectives and motoneuron ISN pioneers (aCC, pCC and RP2 - color coded as in (a) locate in precise positions of the neuropile and project axons with stereotyped trajectories. In puc mutants or after overexpressing HepCA, their positions are altered (mostly the RP2) and the paths of their axons distorted42 (Stage 14 Pioneers). This results in the repositioning of followers (magenta in the wild type and yellow in mutant conditions), adapting to the aberrant axonal landscape (Stage 14 Pioneers and Followers). One secondary effect of the disorganization of the architecture of the VNC, along other defects in neuron/glia interactions, is its failure to condense (Stage 17).
Back To Top