Extracellular Matrix Components HAPLN1, Lumican, and Collagen I Cause Hyaluronic Acid-Dependent Folding of the Developing Human Neocortex

Neocortical expansion, thought to underlie the cognitive traits unique to humans, is accompanied by cortical folding. This folding starts around gestational week (GW) 20, but what causes it remains largely unknown. Extracellular matrix (ECM) has been previously implicated in neocortical expansion an...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2018-08, Vol.99 (4), p.702-719.e6
Main Authors: Long, Katherine R., Newland, Ben, Florio, Marta, Kalebic, Nereo, Langen, Barbara, Kolterer, Anna, Wimberger, Pauline, Huttner, Wieland B.
Format: Article
Language:English
Subjects:
Animals
Cognitive ability
Collagen
Collagen (type I)
Collagen Type I - analysis
Collagen Type I - metabolism
ECM
Experiments
Extracellular matrix
Extracellular Matrix - chemistry
Extracellular Matrix - drug effects
Extracellular Matrix - metabolism
Extracellular Matrix Proteins - analysis
Extracellular Matrix Proteins - metabolism
Female
Ferrets
Fetal Development - drug effects
Fetal Development - physiology
Fetuses
Gene expression
HAPLN1
Human neocortex
Humans
Hyaluronic acid
Hyaluronic Acid - pharmacology
lumican
Lumican - analysis
Lumican - metabolism
Mice
Mice, Inbred C57BL
Microscopy
Neocortex
Neocortex - chemistry
Neocortex - drug effects
Neocortex - growth & development
Neocortex - metabolism
neocortex development
neocortex folding
Neurodevelopmental disorders
Neurogenesis
Neurons
Organ Culture Techniques
Pregnancy
Proteoglycans - analysis
Proteoglycans - metabolism
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Summary:Neocortical expansion, thought to underlie the cognitive traits unique to humans, is accompanied by cortical folding. This folding starts around gestational week (GW) 20, but what causes it remains largely unknown. Extracellular matrix (ECM) has been previously implicated in neocortical expansion and here we investigate the potential role of ECM in the formation of neocortical folds. We focus on three specific ECM components localized in the human fetal cortical plate (CP): hyaluronan and proteoglycan link protein 1 (HAPLN1), lumican and collagen I (collectively, HLC). Addition of HLC to cultures of human fetal neocortex (11–22 GW) caused local changes in tissue stiffness, induced CP folding, increased CP hyaluronic acid (HA), and required the HA-receptor CD168 and downstream ERK signaling. Importantly, loss of HA reduced HLC-induced and 22 GW physiological nascent folds. This was altered in samples with neurodevelopmental disorders, indicating it may be a useful system to study such disorders. [Display omitted] •ECM components HAPLN1, lumican and collagen I (HLC) induce human neocortex folding•HLC-induced folding involves increases in ECM stiffness and requires HA/CD168/ERK•Degradation of HA reduces physiological folds in 22 GW human neocortex•HLC-induced cortical folding is impaired in certain neurodevelopmental disorders Folding of the human neocortex is a key feature of its evolutionary expansion. Here, Long et al. identify a novel extracellular matrix-driven mechanism underlying human neocortex folding, and disruption of this mechanism perturbs the physiological folding of human neocortical tissue.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2018.07.013