Neurogenesis at the Brain–Cerebrospinal Fluid Interface

Lehtinen, Maria K.; Walsh, Christopher A.

doi:10.1146/annurev-cellbio-092910-154026

Cited by 187 publications

(205 citation statements)

References 205 publications

(264 reference statements)

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“…Notably, Sema3B is not restricted to the floor plate but is also synthesized by the choroid plexi in the brain. The CSF is known to convey several patterning and growth-promoting cues for neural progenitor cells in developing and adult brains 53 . Thus, our work opens new lines of investigations and further enlarge the spectrum of neurogenesis processes that could be physiologically and artificially targeted through the CSF.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis

et al. 2015

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The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis. Here we analysed neuroepithelial progenitors in the developing mouse spinal cord to determine whether extracellular signals orient the mitotic spindle. We report that Semaphorin3B (Sema3B) released from the floor plate and the nascent choroid plexus in the cerebrospinal fluid (CSF) controls progenitor division orientation. Delivery of exogenous Sema3B to neural progenitors after neural tube opening in living embryos promotes planar orientation of their division. Preventing progenitor access to cues present in the CSF by genetically engineered canal obstruction affects the proportion of planar and oblique divisions. Sema3B knockout phenocopies the loss of progenitor access to the CSF. Sema3B binds to the apical surface of mitotic progenitors and exerts its effect via Neuropilin receptors, GSK3 activation and subsequent inhibition of the microtubule stabilizer CRMP2. Thus, extrinsic control mediated by the Semaphorin signalling orients progenitor divisions in neurogenic zones.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis

et al. 2015

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“…The embryonic cerebrospinal fluid is a rich and dynamic source of growth factors for the brain, producing and distributing diffusible signals such as FGF, insulin-like growth factor, sonic hedgehog (Shh), and retinoic acid. Therefore, the embryonic cerebrospinal fluid forms an integral component of the embryonic stem cell niche (Lehtinen and Walsh, 2011). The active role of the cerebrospinal fluid in the adult CNS, especially in the adult spinal cord and cauda equina, is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of neonatal dorsal root ganglion-derived neural stem cells into oligodendrocytes after intrathecal transplantation into a cauda equina lesion model

Fu¹,

Shi²,

Liu³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Cauda equina syndrome (CES) is characterized by varying patterns of low back pain, sciatica, lower extremity sensorimotor loss, and bowel and bladder dysfunction. The prognosis for complete recovery of CES is dependent on not only the time before surgical intervention with decompression but also the severity of the nerve damage. Delayed or severe nerve compression impairs the capability of nerve regeneration. Transplantation of neural stem cells (NSCs) may facilitate axon regeneration and functional recovery in a spectrum of neurological disorders. Our study shows that the NSCs derived from early postnatal dorsal root ganglion (DRG) are able to proliferate to form neurospheres and differentiate into O4 + oligodendrocytes but not glial fibrillary acidic protein (GFAP Stem cells grafted into a cauda equina lesion model recovery of sensorimotor function was not significantly improved in rats with transplantation therapy, our results implied that subarachnoid microinjection of NSCs may promote axon regeneration of DRG neurons in the cauda equina model after nerve injury.

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“…Hem ablation had less obvious effects on indicators of BMP signaling, possibly because BMP ligands are secreted by choroid plexus epithelium (CPe), and are available to ventricular zone (VZ) progenitor cells from embryonic cerebrospinal fluid (Lehtinen and Walsh, 2011;Marques et al, 2011). Lack of WNT signaling from the hem caused loss of the adjacent hippocampus, whereas lack of hem BMPs only reduced the adjacent CPe (Yoshida et al, 2006).…”

Section: Reduced Indicators Of Wnt and Bmp Signaling In Hemablated Micementioning

confidence: 99%

The cortical hem regulates the size and patterning of neocortex

et al. 2014

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The cortical hem, a source of Wingless-related (WNT) and bone morphogenetic protein (BMP) signaling in the dorsomedial telencephalon, is the embryonic organizer for the hippocampus. Whether the hem is a major regulator of cortical patterning outside the hippocampus has not been investigated. We examined regional organization across the entire cerebral cortex in mice genetically engineered to lack the hem. Indicating that the hem regulates dorsoventral patterning in the cortical hemisphere, the neocortex, particularly dorsomedial neocortex, was reduced in size in latestage hem-ablated embryos, whereas cortex ventrolateral to the neocortex expanded dorsally. Unexpectedly, hem ablation also perturbed regional patterning along the rostrocaudal axis of neocortex. Rostral neocortical domains identified by characteristic gene expression were expanded, and caudal domains diminished. A similar shift occurs when fibroblast growth factor (FGF) 8 is increased at the rostral telencephalic organizer, yet the FGF8 source was unchanged in hem-ablated brains. Rather we found that hem WNT or BMP signals, or both, have opposite effects to those of FGF8 in regulating transcription factors that control the size and position of neocortical areas. When the hem is ablated a necessary balance is perturbed, and cerebral cortex is rostralized. Our findings reveal a much broader role for the hem in cortical development than previously recognized, and emphasize that two major signaling centers interact antagonistically to pattern cerebral cortex.

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Neurogenesis at the Brain–Cerebrospinal Fluid Interface

Cited by 187 publications

References 205 publications

Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis

Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis

Differentiation of neonatal dorsal root ganglion-derived neural stem cells into oligodendrocytes after intrathecal transplantation into a cauda equina lesion model

The cortical hem regulates the size and patterning of neocortex

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