Abstract
Neurons reach their correct targets by directional outgrowth of axons, which is mediated by attractive or repulsive cues. Growing axons occasionally cross a field of repulsive cues and stop at intermediate targets on the journey to their final destination. However, it is not well-understood how individual growth cones make decisions, and pass through repulsive territory to reach their permissive target regions. We developed a microcontact printing culture system that could trap individual axonal tips in a permissive dot area surrounded by the repulsive signal, semaphorin 3F (Sema3F). Axons of rat hippocampal neurons on the Sema3F/PLL dot array extended in the checkboard pattern with a significantly slow growth rate. The detailed analysis of the behaviors of axonal growth cones revealed the saccadic dynamics in the dot array system. The trapped axonal tips in the permissive area underwent growth cone enlargement with remarkably spiky filopodia, promoting their escape from the Sema3F constraints with straight extension of axons. This structured axonal growth on the dot pattern was disrupted by increased inter-dot distance, or perturbing intracellular signaling machineries. These data indicate that axons grow against repulsive signals by jumping over the repulsive cues, depending on contact signals and intracellular milieu. Our study suggests that our dot array culture system can be used as a screening system to easily and efficiently evaluate ECM or small molecule inhibitors interfering growth cone dynamics leading to controlling axonal growth.
| Original language | English |
|---|---|
| Pages (from-to) | 291-305 |
| Number of pages | 15 |
| Journal | Lab on a chip |
| Volume | 19 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2019 Jan 1 |
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ASJC Scopus subject areas
- Bioengineering
- Biochemistry
- Chemistry(all)
- Biomedical Engineering
Cite this
A monitoring system for axonal growth dynamics using micropatterns of permissive and Semaphorin 3F chemorepulsive signals. / Ryu, Jae Ryun; Kim, June Hoan; Cho, Hyo Min; Jo, Youhwa; Lee, Boram; Joo, Sunghoon; Chae, Uikyu; Nam, Yoonkey; Cho, Il Joo; Sun, Woong.
In: Lab on a chip, Vol. 19, No. 2, 01.01.2019, p. 291-305.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A monitoring system for axonal growth dynamics using micropatterns of permissive and Semaphorin 3F chemorepulsive signals
AU - Ryu, Jae Ryun
AU - Kim, June Hoan
AU - Cho, Hyo Min
AU - Jo, Youhwa
AU - Lee, Boram
AU - Joo, Sunghoon
AU - Chae, Uikyu
AU - Nam, Yoonkey
AU - Cho, Il Joo
AU - Sun, Woong
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Neurons reach their correct targets by directional outgrowth of axons, which is mediated by attractive or repulsive cues. Growing axons occasionally cross a field of repulsive cues and stop at intermediate targets on the journey to their final destination. However, it is not well-understood how individual growth cones make decisions, and pass through repulsive territory to reach their permissive target regions. We developed a microcontact printing culture system that could trap individual axonal tips in a permissive dot area surrounded by the repulsive signal, semaphorin 3F (Sema3F). Axons of rat hippocampal neurons on the Sema3F/PLL dot array extended in the checkboard pattern with a significantly slow growth rate. The detailed analysis of the behaviors of axonal growth cones revealed the saccadic dynamics in the dot array system. The trapped axonal tips in the permissive area underwent growth cone enlargement with remarkably spiky filopodia, promoting their escape from the Sema3F constraints with straight extension of axons. This structured axonal growth on the dot pattern was disrupted by increased inter-dot distance, or perturbing intracellular signaling machineries. These data indicate that axons grow against repulsive signals by jumping over the repulsive cues, depending on contact signals and intracellular milieu. Our study suggests that our dot array culture system can be used as a screening system to easily and efficiently evaluate ECM or small molecule inhibitors interfering growth cone dynamics leading to controlling axonal growth.
AB - Neurons reach their correct targets by directional outgrowth of axons, which is mediated by attractive or repulsive cues. Growing axons occasionally cross a field of repulsive cues and stop at intermediate targets on the journey to their final destination. However, it is not well-understood how individual growth cones make decisions, and pass through repulsive territory to reach their permissive target regions. We developed a microcontact printing culture system that could trap individual axonal tips in a permissive dot area surrounded by the repulsive signal, semaphorin 3F (Sema3F). Axons of rat hippocampal neurons on the Sema3F/PLL dot array extended in the checkboard pattern with a significantly slow growth rate. The detailed analysis of the behaviors of axonal growth cones revealed the saccadic dynamics in the dot array system. The trapped axonal tips in the permissive area underwent growth cone enlargement with remarkably spiky filopodia, promoting their escape from the Sema3F constraints with straight extension of axons. This structured axonal growth on the dot pattern was disrupted by increased inter-dot distance, or perturbing intracellular signaling machineries. These data indicate that axons grow against repulsive signals by jumping over the repulsive cues, depending on contact signals and intracellular milieu. Our study suggests that our dot array culture system can be used as a screening system to easily and efficiently evaluate ECM or small molecule inhibitors interfering growth cone dynamics leading to controlling axonal growth.
UR - http://www.scopus.com/inward/record.url?scp=85060047071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060047071&partnerID=8YFLogxK
U2 - 10.1039/c8lc00845k
DO - 10.1039/c8lc00845k
M3 - Article
C2 - 30539180
AN - SCOPUS:85060047071
VL - 19
SP - 291
EP - 305
JO - Lab on a Chip - Miniaturisation for Chemistry and Biology
JF - Lab on a Chip - Miniaturisation for Chemistry and Biology
SN - 1473-0197
IS - 2
ER -