The cerebrospinal fluid provides a proliferative niche for neural progenitor cells

By Maria K. Lehtinen, Mauro W. Zappaterra, X. Chen, Yawei J. Yang, Anthony D. Hill, Melody P. Lun, T. Maynard, Dilenny M. Gonzalez, Seonhee Kim, P. Ye and 4 more. Neuron, 2011

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Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/98c099e44e52a690e7a089c34e365931dd019f20

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Citations in the corpus

The many faces of insulin-like peptide signalling in the brain (2012, background): “A recent study described an important role of IGFs from the CSF in proliferation of cortical progenitor”
Single-Cell Profiling and SCOPE-Seq Reveal Lineage Dynamics of Adult Ventricular-Subventricular Zone Neurogenesis and NOTUM as a Key Regulator (2020, positive): “The mouse adult V-SVZ is continuously exposed to proliferative WNT ligands in cerebrospinal fluid (Lehtinen et al., 2011) and the V-SVZ niche (Figure S3F).”
The cell biology of neurogenesis: toward an understanding of the development and evolution of the neocortex. (2014, background): “…is important to consider these cell polarity features in the context of tissue polarity, as certain proliferative or differentiative signals may be conveyed via the ventricular fluid or the basal lamina ( Johansson et al. 2010, Lehtinen & Walsh 2011, Lehtinen et al. 2011, Siegenthaler et al. 2009).”
Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later (2015, background): “While its role remains to be characterized for adult NSCs, CSF in the embryonic brain promotes cortical neural progenitor proliferation via IGF-2 (Lehtinen et al., 2011).”
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders (2011, background): “During embryonic development of the neural tube, blood vessels and choroid plexus secrete IGF2 into the CSF, which regulates the proliferation of neuronal progenitor cell”
Molecular Identity of Human Outer Radial Glia During Cortical Development (2015, positive): “Apical complex proteins transduce signals from the cerebrospinal fluid that are critical for the survival, proliferation, and neurogenic capacity of ventricular radial glia (vRG) (Lehtinen et al., 2011).”
Spatiotemporal transcriptome of the human brain (2011, background): “) and IGF2 (an imprinted autosomal gene previously implicated in embryonic growth and cognitive functio”