# Sequoia affects Drosophila central nervous system development by regulating axonal extension and guidance

**Authors:** Noor Al-Hajri, Raquel Mendez-Castro, Mar Alujas, Sofia J. Araújo, Guy Tear, Renping Zhou, Renping Zhou, Renping Zhou, Renping Zhou

PMC · DOI: 10.1371/journal.pone.0333573 · PLOS One · 2026-03-25

## TL;DR

This paper shows that the Sequoia protein influences Drosophila nervous system development by affecting axon growth and guidance.

## Contribution

The study identifies new sequoia alleles and reveals a role for Sequoia in linking neuronal differentiation to axonal development.

## Key findings

- seq mutations cause defects in CNS spatial organization and cell morphology.
- Sequoia affects motor axon outgrowth and CNS/PNS development.
- Different Seq domains are important for nervous system development.

## Abstract

The development of the Drosophila melanogaster central nervous system (CNS) requires both determination of neuronal cell types and the subsequent establishment of neural connectivity. Numerous studies have identified genes and molecules required for both these processes. Once neurons have differentiated, they are guided to their targets by attractive and repulsive forces and an increasing number of molecules that provide these functions have been identified. However, little is known on how molecules involved in neuronal differentiation might affect subsequent steps of axonal development such as axonal morphogenesis. The sequoia (seq) mutant was identified in a Drosophila genetic screen for defects in dendrite elaboration. Sequoia is a pan-neural nuclear protein containing two putative zinc-fingers homologous to the DNA binding domain of Tramtrack. Mutations in seq have been reported to affect the cell fate decision of external sensory organ neurons and to effect axon and dendrite morphology. Previous reports have focused mainly on the effects this mutation causes in dendritic morphogenesis in the peripheral nervous system (PNS). Amongst mutants isolated from a previous mutagenesis screen, we have identified three new alleles of sequoia, GA168, C022 and C3101 and identify the molecular lesions in two previously identified alleles, Z1241 and H156. Analysis of these five alleles has revealed that seq mutations lead to several defects in nervous system development. seq mutants show defects in the spatial organization of their CNS from early developmental stages and have abnormal cell morphology, both at early and late stages of embryonic development. Mutations in seq affect motor axon outgrowth and general CNS and PNS development. The reported seq mutations reveal an important link between neuronal differentiation and axonal outgrowth and guidance and shed light on the importance of different Seq domains.

## Linked entities

- **Genes:** seq (sequoia) [NCBI Gene 3772396]
- **Species:** Drosophila melanogaster (taxon 7227)

## Full-text entities

- **Genes:** seq (sequoia) [NCBI Gene 3772396] {aka 2R5, 49Fc, CG17724b, CG32904, CG4037, CG4055}, Fas2 (Fasciclin 2) [NCBI Gene 31364] {aka 1D4, Ab 1D4, CG3665, CT12301, Dmel\CG3665, EG:EG0007.3}, ttk (tramtrack) [NCBI Gene 48317] {aka 0037/17, 0250/25, 0438/31, 0702/07, 1049/07, 1119/04}, eve (even skipped) [NCBI Gene 36039] {aka 10.5, 10.9, 14.10, 20.35, CG2328, Dm-eve}, Sema2b (Semaphorin 2b) [NCBI Gene 246538] {aka CG30322, CG33960, CG4383, Dmel\CG33960, Sema-2b, SemaIIB}, rpr (reaper) [NCBI Gene 40015] {aka CG4319, Dmel\CG4319, Reaper, anon-WO0162936.19, rp}, ABC [NCBI Gene 49225], Myc (Myc) [NCBI Gene 31310] {aka CG10798, D-Myc, DM, DMYc, Diminutive, Dm}, hrp (hyperpolarizing receptor potential) [NCBI Gene 43883], grim (grim) [NCBI Gene 40014] {aka BcDNA:RE28551, CG4345, Dmel\CG4345, gri, grm}, hid (head involution defective) [NCBI Gene 40009] {aka CG5123, Dmel\CG5123, Hid1, W, hid1, his}, Fas3 (Fasciclin 3) [NCBI Gene 35097] {aka CG5803, Dmel\CG5803, FAS III, FASIII, Fas, Fas III}
- **Diseases:** embryonic lethality (MESH:D020964)
- **Chemicals:** glycerol (MESH:D005990), DAB (-), formaldehyde (MESH:D005557), PBS (MESH:D007854)
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** Q76X, (CAG) at position 739, (AAA) at position 452, stop codon at amino acid 76, Q739X, (CAG) at position 559, Q713X
- **Cell lines:** seqGA168 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0I84), H156 — Homo sapiens (Human), Transformed cell line (CVCL_6G68)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13016347/full.md

## References

24 references — full list in the complete paper: https://tomesphere.com/paper/PMC13016347/full.md

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Source: https://tomesphere.com/paper/PMC13016347