New Neurons Follow the Flow of Cerebrospinal Fluid in the Adult Brain

Sawamoto, Kazunobu; Wichterle, Hynek; González-Pérez, Óscar; Cholfin, Jeremy A.; Yamada, Masayuki; Spassky, Nathalie; Murcia, Noel S.; García‐Verdugo, José Manuel; Marı́n, Oscar; Rubenstein, John L.R.; Tessier‐Lavigne, Marc; Okano, Hideyuki; Alvarez-Buylla, Arturo

doi:10.1126/science.1119133

Cited by 701 publications

(621 citation statements)

References 19 publications

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“…The role of CSF in the regulation of the adult neural stem cell is unknown, but recently it has been shown that the flow of the CSF generated by the ciliated ependymal cells in the adult CNS is critical in establishing a gradient of molecules (such as slit), which play a role in the directional migration of their daughter neuroblasts (Sawamoto et al, 2006).…”

Section: Signaling In Adult Neural and Other Stem Cell Nichesmentioning

confidence: 99%

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

Lathia

Rao

Mattson

et al. 2007

Developmental Dynamics

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A better understanding of the signals regulating embryonic neural stem cells is clearly an important goal. However, many studies on neural stem cell biology are conducted on the slowly-dividing cells found in the adult CNS, where specialized microenvironments or niches maintain the stem cells throughout life. By contrast, the embryonic VZ is a transient structure that does not fulfill the criteria conventionally used to define niches. In this review we will examine whether, despite these differences, the signals found in other adult stem cell niches are present in the VZ. Using the similarities and differences we observe, we will reconsider whether the location of embryonic stem cell populations such as the VZ can be thought of as niches. Finally, we will ask how these lessons from the niche inform our understanding of neurodevelopmental diseases and cancers of the CNS. Developmental Dynamics 236:3267-3282, 2007.

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Section: Signaling In Adult Neural and Other Stem Cell Nichesmentioning

confidence: 99%

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

Lathia

Rao

Mattson

et al. 2007

Developmental Dynamics

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“…In addition, two rodent models for hydrocephalus (the WIC-Hyd rat and SUMS/ NP mouse) have ciliary defects although the mutated genes are not currently known [Bruni et al, 1988;Torikata et al, 1991]. Intriguingly a very recent report indicates that cerebrospinal fluid flow, driven by the motile cilia of ependymal cells, establishes a chemical gradient within the subventricular zone, and is required for the correct migration of neuroblasts in adult mouse brain [Sawamoto et al, 2006]. This suggests a further mechanism by which defects in ependymal ciliary motility might have a direct effect on neuronal development.…”

Section: Efhc1 Mutations and Juvenile Myoclonic Epilepsymentioning

confidence: 99%

Axonemal protofilament ribbons, DM10 domains, and the link to juvenile myoclonic epilepsy

King

2006

Cell Motil. Cytoskeleton

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Juvenile myoclonic epilepsy (JME) is a common neurological disorder that results in short uncontrolled muscle contractions and sometimes more severe seizures. Genetic studies have suggested that JME may be caused by mutations in EFHC1. The Efhc1 protein consists of three DM10 domains and a C-terminal region containing a potential Ca 2þ -binding motif. In Chlamydomonas, a protein (Rib72) of almost identical domain structure is a component of the protofilament ribbons within the doublet microtubules of the flagellar axoneme. Here I discuss recent work that supports assignment of human Efhc1 as a ciliary component and the resulting implications for the mechanism of disease causation. Cell Motil.

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“…Directional migration cues, which are relevant following neural injury, include members of the chemokine family, such as CXCL12/CXCR4 [14][15][16]. Axon guidance molecules, such as Slits [17,18] and other factors [19,20], also play a role in the directed NPC migration along the RMS, along with chemoattractive agents secreted from the OB such as sonic hedgehog [21] or secreted or membranebound factors on the astrocytic glial tube that surrounds the NPCs in the RMS [22,23].…”

Section: Introductionmentioning

confidence: 99%

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

et al. 2011

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Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB). Following neural injury, they also migrate to the site of damage. This study investigated the role of Rho-dependent kinase (ROCK) on the migration of NPCs in vitro and in vivo. In vitro, using neurospheres or SVZ explants, inhibition of ROCK using Y27632 promoted cell body elongation, process protrusion, and migration, while inhibiting NPC chain formation. It had no effect on proliferation, apoptosis, or differentiation. Both isoforms of ROCK were involved. Using siRNA, knockdown of both ROCK1 and ROCK2 was required to promote NPC migration and morphological changes; knockdown of ROCK2 alone was partially effective, with little/no effect of knockdown of ROCK1 alone. In vivo, infusion of Y27632 plus Bromodeoxyuridine (BrdU) into the lateral ventricle for 1 week reduced the number of BrdU-labeled NPCs in the OB compared with BrdU infusion alone. However, ROCK inhibition did not affect the tangential-to-radial switch of NPC migration, as labeled cells were present in all OB layers. The decrease in NPC number at the OB was not attributed to a decrease in NPCs at the SVZ. However, ROCK inhibition decreased the density of BrdU-labeled cells in the RMS and increased the distribution of these cells to ectopic brain regions, such as the accessory olfactory nucleus, where the majority differentiated into neurons. These findings suggest that ROCK signaling regulates NPC migration via regulation of cell-cell contact and chain migration.

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New Neurons Follow the Flow of Cerebrospinal Fluid in the Adult Brain

Cited by 701 publications

References 19 publications

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

Axonemal protofilament ribbons, DM10 domains, and the link to juvenile myoclonic epilepsy

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

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