Evidence map›Paper›PMID 30893602›Full record

ArticleCell reports2019

Ndfip Proteins Target Robo Receptors for Degradation and Allow Commissural Axons to Cross the Midline in the Developing Spinal Cord.

Madhavi Gorla, Celine Santiago, Karina Chaudhari, Awo Akosua Kesewa Layman, Paula M Oliver, Greg J Bashaw

Abstract read
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

  1. Article
  2. Gene expression programs underlying spinal commissural neuron differentiation and axon growth across the midline.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. CD47 stabilizes ROBO2 to regulate glioblastoma progression by preventing ITCH-mediated ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Emerging roles for E3 ubiquitin ligases in neural development and disease.Frontiers in cell and developmental biology · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Structure and evolution of neuronal wiring receptors and ligands.Developmental dynamics : an official publication of the American Association of Anatomists · 2023
    Review
  18. Article
  19. Transcriptional Control of Axon Guidance at Midline Structures.Frontiers in cell and developmental biology · 2022
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Madhavi GorlaDepartment of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Celine SantiagoDepartment of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Karina ChaudhariDepartment of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Awo Akosua Kesewa LaymanThe Children's Hospital of Philadelphia, Division of Protective Immunity, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USA.
Paula M OliverThe Children's Hospital of Philadelphia, Division of Protective Immunity, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USA.
Greg J BashawDepartment of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: gbashaw@pennmedicine.upenn.edu.

Funding

Molecular mechanisms of axon guidance receptor regulation and signalingR35NS097340 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI BASHAW, GREG J. · 2017 to 2024
$5.8M
NINDS NIH HHS R35 NS097340
6 · The paper itself

Abstract

Commissural axons initially respond to attractive signals at the midline, but once they cross, they become sensitive to repulsive cues. This switch prevents axons from re-entering the midline. In insects and mammals, negative regulation of Roundabout (Robo) receptors prevents premature response to the midline repellant Slit. In Drosophila, the endosomal protein Commissureless (Comm) prevents Robo1 surface expression before midline crossing by diverting Robo1 into late endosomes. Notably, Comm is not conserved in vertebrates. We identified two Nedd-4-interacting proteins, Ndfip1 and Ndfip2, that act analogously to Comm to localize Robo1 to endosomes. Ndfip proteins recruit Nedd4 E3 ubiquitin ligases to promote Robo1 ubiquitylation and degradation. Ndfip proteins are expressed in commissural axons in the developing spinal cord and removal of Ndfip proteins results in increased Robo1 expression and reduced midline crossing. Our results define a conserved Robo1 intracellular sorting mechanism between flies and mammals to avoid premature responsiveness to Slit.

Indexed as

AnimalsAxonsChlorocebus aethiopsCOS CellsDrosophilaDrosophila ProteinsHeLa CellsHumansIntercellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, KnockoutNedd4 Ubiquitin Protein LigasesNerve Tissue ProteinsProteolysisReceptors, Immunologiccomm protein, DrosophilaDrosophila ProteinsIntercellular Signaling Peptides and ProteinsMembrane ProteinsNdfip1 protein, mouseNDFIP2 protein, mouseNedd4 Ubiquitin Protein LigasesNerve Tissue ProteinsReceptors, ImmunologicRoundabout Proteinsaxon guidanceCommissurelessE3 ubiquitin ligasemidlineNdfipNedd4repulsionRoboSlitspinal cord

Identifiers

PMID30893602
PMCPMC6913780

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.