# Novel functions of Plxdc1 in neurite formation

> **NIH NIH F31** · DREXEL UNIVERSITY · 2020 · $35,680

## Abstract

Proposal Summary/Abstract
Neural circuits undergo neurite outgrowth in response to seizures, leading to aberrant axonal sprouting and
changes to the morphology and connectivity of mature neurons. Thus, neurite growth inhibitory factors could
have clinical applications. Only about one third of patients with epilepsy can control seizures using current
antiepileptic drugs, so identification of new therapeutic targets is crucial, yet challenging, since neurite
formation remains poorly understood. Here, we propose a function for plexin domain containing 1 (Plxdc1) in
regulating neurite initiation and elongation via the potentially downstream kinases Akt and FAK. Plxdc1 is a
single transmembrane domain receptor embedded in the plasma membrane and its downstream signaling
pathway is currently unknown. Previously, microRNA targeting Plxdc1 has been shown to be inversely
correlated with epileptogenesis. Plxdc1 serves as a receptor for nidogen-1 and PEDF. Disruption of nidogen-1
leads to seizure-like symptoms, while deletion of PEDF may contribute to the etiology of Miller-Dieker
Syndrome, which is strongly associated with epilepsy. Interestingly, we observed that Plxdc1 overexpression
(OE) drives the formation of neurite-like extensions in N2a cells. Plxdc1 OE in primary cortical neurons led to
increased dendrite length, while Plxdc1 knockdown led to fewer and shorter dendrites. We confirmed these
phenotypes in vivo by using in utero electroporation. We conducted a high-throughput kinase inhibitor library
screening in which N2a cells undergoing Plxdc1-OE-driven neurite formation were treated with 493 kinase
inhibitors. Based on an initial analysis of results, we hypothesize that Plxdc1 signals via the downstream
kinases Akt and FAK to modulate neurite initiation and elongation. Since cytoskeletal dynamics drive the
morphological changes that occur during neurite formation, we will investigate how Plxdc1 signaling regulates
actin aggregation and microtubule stability. This work will advance our understanding of a fundamental process
in normal brain development and may have implications for therapeutic roles in treating epilepsy. Further work
is necessary to determine how changes in Plxdc1 expression impact neuronal connectivity and networks.

## Key facts

- **NIH application ID:** 10067668
- **Project number:** 1F31NS113404-01A1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Sara M Blazejewski
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $35,680
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067668

## Citation

> US National Institutes of Health, RePORTER application 10067668, Novel functions of Plxdc1 in neurite formation (1F31NS113404-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10067668. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*