Sagittal view of a rodent brain (a) depicting the endogenous rostral migratory stream (b). neural precursor cells continue to be produced in the subventricular zone of most adult mammals. These cells can mature into neuroblasts and migrate in chains along the pathway of aligned astrocytes that comprise the rostral migratory stream to arrive at the olfactory bulb. In the presence of a lesion, neuroblasts divert from the endogenous SVZ/RMS and migrate toward the lesion, but their numbers are not sufficient to improve functional recovery (c). The TE-RMS is comprised of tight bundles of longitudinally aligned astrocytes within a hydrogel microcolumn. Immature neurons seeded on one end of the TE-RMS migrate as chains through the TE-RMS in vitro (d). Migrating neurons release Slit1, which is recognized by the Robo2 receptors that are expressed by the astrocytes comprising the TE-RMS (e). This chemorepellent communication allows the neuroblasts to efficiently migrate through the aligned astrocyte network and serves as one example of the dynamic two-way communication that occurs in the endogenous RMS. The TE-RMS can be extracted from its hydrogel microcolumn and implanted into the rodent brain to span the distance between the SVZ/RMS and the lesion (f). Proof-of-principle evidence suggests that neuroblasts will divert from the SVZ/RMS and migrate in chain formation through the implanted TE-RMS (g). Based on existing literature, we predict that over time redirected neuroblasts will mature into phenotype-relevant mature neurons in lesioned regions and integrate into existing circuitry (h). This diagram was created with BioRender.com.
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