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A stem cell-derived neuronal culture model for mouse species variation in neurite growth

ABSTRACT: Stem cell-derived neurons represent a powerful experimental system for the study of axon growth and regeneration, cutting cost and technical challenges. We developed an in vitro system using stem cell-derived motor neurons to investigate phenotypic differences in neurite growth between mouse subspecies. Previously, neurons in CAST/EiJ mice (Mus musculus castaneus) were reported to regrow CNS axons after injury to a greater degree than other strains. Here, we assayed neurite outgrowth from stem cell-neurons in a fully in vitro system, in the abscence of injury signals. In this system, CAST/EiJ neurons grew longer axons than those of C57BL/6J and 129S6/SvEv origin. Additionally, CASTx129 hybrid neurons exhibit comparable neurite growth to CAST/EiJ, indicating a dominant genetic effect.

ORGANISM(S): Mus musculus domesticus Mus musculus Mus musculus castaneus

PROVIDER: GSE304838 | GEO | 2026/04/06

REPOSITORIES: GEO

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A stem cell-derived neuronal culture model for mouse species variation in neurite growth

Project description:Stem cell-derived neurons represent a powerful experimental system for the study of axon growth and regeneration, cutting cost and technical challenges. We developed an in vitro system using stem cell-derived motor neurons to investigate phenotypic differences in neurite growth between mouse subspecies. Previously, neurons in CAST/EiJ mice (Mus musculus castaneus) were reported to regrow CNS axons after injury to a greater degree than other strains. Here, we assayed neurite outgrowth from stem cell-neurons in a fully in vitro system, in the abscence of injury signals. In this system, CAST/EiJ neurons grew longer axons than those of C57BL/6J and 129S6/SvEv origin. Additionally, CASTx129 hybrid neurons exhibit comparable neurite growth to CAST/EiJ, indicating a dominant genetic effect.

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Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

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Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

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Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling

Project description:We screened nine genetically diverse inbred mouse strains for differences in axonal growth of adult dorsal root ganglion (DRG) neurons on CNS myelin. Naïve DRG neurite outgrowth on myelin was very limited, but preconditioning the neurons by a prior sciatic nerve crush increased axonal growth substantially across all strains, with by far the greatest change in neurons from CAST/Ei mice. Three independent in vivo CNS injury models revealed greater capacity for CNS axonal regeneration in CAST/Ei than C57BL/6 mice. Full-genome expression profiling of naïve and pre-conditioned DRGs across all strains revealed Activin-βA (Inhba) as the transcript whose expression most closely correlated with axonal growth on myelin. In vitro and in vivo gain- and loss-of-function experiments confirmed that Activin promotes axonal growth in the CNS. Substantial regeneration is possible, therefore, in the injured mammalian CNS when Activin signaling is intrinsically high, as in CAST/Ei or when extrinsically modulated in other strains. 9 strains, 4 replicates per strain, 2 conditions (naïve and axotomy) = 72 samples. 2 samples were excluded because technical outliers (AJ_AX5D_1 and AJ_NAIVE_4 excluded from the normalized data but included in the raw data)

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Transcription profiling of mouse rat cortical axons from un-injured and injured animals isolated after 13 days in culture

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Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling

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