Research discovers growth cone aids neuronal migration and brain regeneration post-injury

Postnatal mammalian brains contain neural stem cells that generate new neurons. These neurons migrate towards injured areas, and enhancing this migration aids functional recovery after brain injury. However, inhibitory effects on migration at injury sites need clarification to improve neuron recruitment and enhance recovery. Migrating neurons exhibit axonal growth cone-like structures at their tips, yet their role in migration remains partially understood.

The group examined the role of the growth cone-like structure in migrating mouse brain neurons. Using super-resolution microscopy, they studied its cytoskeletal dynamics and molecular features, revealing its similarity to axonal growth cones. Specifically, the growth cone responds to external signals via tyrosine phosphatase receptor type sigma (PTPσ), guiding migration directionality and initiating cell body movement. Chondroitin sulfate (CS) interaction with PTPσ causes growth cone collapse, inhibiting migration, while heparan sulfate (HS) interaction restores its extended morphology, enabling migration.

Further, they employed HS-containing gelatin-fiber non-woven fabric, a biomaterial offering structural scaffolding for cells like migrating neurons. Demonstrating that these fibers encouraged growth cone extension and neuronal migration in injured brains, they also found that implanting the HS-enriched gelatin fabric facilitated mature neuron regeneration and neurological function restoration. These findings imply that understanding the molecular mechanisms of growth cone interaction with the local extracellular environment may lead to innovative regeneration technologies promoting neuronal migration.

“To investigate whether the effect of HS in reversing the inhibitory effect of CS can promote neuronal migration in the injured brain, it was necessary to apply HS-containing biomaterial to the CS-rich injured brain,” said Sawamoto.

“Given that the growth cone of migrating neurons serves as a primer for neuronal migration under inhibitory extracellular conditions, it is necessary to further investigate whether the growth cone-mediated treatment to recruit new neurons from the endogenous source to the damaged sites is also applicable to aged brains,” said Nakajima.

Reference: Chikako Nakajima, Masato Sawada, Erika Umeda, Yuma Takagi, Norihiko Nakashima, Kazuya Kuboyama, Naoko Kaneko, Satoaki Yamamoto, Haruno Nakamura, Naoki Shimada, Koichiro Nakamura, Kumiko Matsuno, Shoji Uesugi, Nynke A. Vepřek, Florian Küllmer, Veselin Nasufović, Hironobu Uchiyama, Masaru Nakada, Yuji Otsuka, Yasuyuki Ito, Vicente Herranz-Pérez, José Manuel García-Verdugo, Nobuhiko Ohno, Hans-Dieter Arndt, …Kazunobu Sawamoto; Journal: Nature Communications; DOI: 10.1038/s41467-024-45825-8