# Role of proteoglycan-mediated trans-axonal signaling in pre-target topographic sorting

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2020 · $391,187

## Abstract

Project summary
 The precise organization of axonal projections into topographic maps is crucial for brain function, espe-
cially in sensory systems. An important developmental mechanism contributing to topographic map formation
is pre-target axon sorting, whereby axons are pre-ordered en route to their target according to their identity
and/or positional origin. In the visual system, for instance, axon sorting occurs along the optic tract, where dor-
sal and ventral retinal axons segregate respectively into the ventral and dorsal branches of the tract before
reaching their brain target. While pre-target axon sorting has an instructive role in topographic mapping, how it
is established during development remains poorly understood. Using the unique transparency and accessibility
of the zebrafish embryo, our studies have shown that topographic order along the optic tract is not established
during initial axon guidance but instead achieved through the selective degeneration of missorted dorsal axons
that have erroneously misrouted along the dorsal branch. Heparan Sulfate (HS), a glycosaminoglycan carried
by Heparan Sulfate Proteoglycans (HSPGs), is required non-cell autonomously for this selective degeneration.
Yet, several questions remain unsolved. How does HS instruct missorted dorsal axons to degenerate while
preserving those correctly elongating along the ventral branch of the tract? Is there a specific HSPG involved?
Which molecular pathway(s) does HS regulate? A key difference between missorted and correctly targeted
dorsal axons is their proximity to ventral pioneer axons. While erroneously navigating along the dorsal branch,
missorted dorsal axons appear in close contact with ventral axons that have already elongated. Moreover, our
preliminary data show that the HSPG glypican-3 (Gpc3) is selectively expressed in ventral RGCs in the mature
retina. Thus, we hypothesize that Gpc3-mediated trans-axonal signaling between ventral pioneer and
missorted dorsal follower retinal axons triggers the degeneration of missorted dorsal axons to estab-
lish pre-target topographic sorting in the visual system. We will test that hypothesis by characterizing the
expression and localization of Gpc3 in ventral retinal ganglion cells and corresponding axons (Aim 1), and by
testing the function of Gpc3 in optic tract sorting in a cell specific manner (Aim 2). Gpc3 at the surface of pio-
neer axons may act as a guidance cue acting directly on missorted dorsal axons to trigger their degeneration,
or as a modulating factor controlling sorting indirectly by regulating a trans-axonal signaling pathway. To gain
insight into which signaling factors might be regulated by Gpc3, we will test whether the semaphorin-neuropilin-
plexin pathway, which is known to regulate axon ordering in other systems, also contributes to optic tract sort-
ing (Aim 3). Altogether, these studies will be the first to determine how trans-axonal signaling between pioneer
and follower axons establi...

## Key facts

- **NIH application ID:** 9832217
- **Project number:** 5R01NS109197-02
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Fabienne Emmanuelle Poulain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,187
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832217

## Citation

> US National Institutes of Health, RePORTER application 9832217, Role of proteoglycan-mediated trans-axonal signaling in pre-target topographic sorting (5R01NS109197-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9832217. Licensed CC0.

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