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

TY - JOUR

T1 - Extracellular Matrix Components HAPLN1, Lumican, and Collagen I Cause Hyaluronic Acid-Dependent Folding of the Developing Human Neocortex

AU - Long, Katherine R.

AU - Newland, Ben

AU - Florio, Marta

AU - Kalebic, Nereo

AU - Langen, Barbara

AU - Kolterer, Anna

AU - Wimberger, Pauline

AU - Huttner, Wieland B.

PY - 2018/8/22

Y1 - 2018/8/22

N2 - 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. 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.

AB - 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. 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.

KW - collagen

KW - ECM

KW - HAPLN1

KW - Human neocortex

KW - hyaluronic acid

KW - lumican

KW - neocortex development

KW - neocortex folding

KW - neurodevelopmental disorders

UR - http://www.scopus.com/inward/record.url?scp=85051631756&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2018.07.013

DO - 10.1016/j.neuron.2018.07.013

M3 - Article

C2 - 30078576

AN - SCOPUS:85051631756

SN - 0896-6273

VL - 99

SP - 702-719.e7

JO - Neuron

JF - Neuron

IS - 4

ER -