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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Katherine R. Long - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Ben Newland - , Leibniz-Institut für Polymerforschung Dresden (Autor:in)
  • Marta Florio - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Nereo Kalebic - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Barbara Langen - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Anna Kolterer - , Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Pauline Wimberger - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Wieland B. Huttner - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)

Abstract

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)702-719.e7
FachzeitschriftNeuron
Jahrgang99
Ausgabenummer4
PublikationsstatusVeröffentlicht - 22 Aug. 2018
Peer-Review-StatusJa

Externe IDs

PubMed 30078576

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • collagen, ECM, HAPLN1, Human neocortex, hyaluronic acid, lumican, neocortex development, neocortex folding, neurodevelopmental disorders