Extracellular Matrix in Human Craniofacial Development

Abstract

The extracellular matrix (ECM) is a highly dynamic amalgamation of structural and signaling molecules whose quantitative and qualitative modifications drive the distinct programmed morphologic changes required for tissues to mature into their functional forms. The craniofacial complex houses a diverse array of tissues, including sensory organs, glands, and components of the musculoskeletal, neural, and vascular systems, alongside several other highly specialized tissues to form the most complex part of the vertebrate body. Through cell-ECM interactions, the ECM coordinates the cell movements, shape changes, differentiation, gene expression changes, and other behaviors that sculpt developing organs. In this review, we focus on several common key roles of the ECM to shape developing craniofacial organs and tissues. We summarize recent advances in our understanding of the ability of the ECM to biochemically and biomechanically orchestrate major events of craniofacial development, and we discuss how dysregulated ECM dynamics contributes to disease and disorders. As we expand our understanding of organ-specific matrix functionality and composition, we will improve our ability to rationally modify matrices to promote regeneration and/or prevent degenerative outcomes in vitro and in vivo.

ExploringWNT2Polymorphisms in Comitant Strabismus: A Genetic Association Study

“…30 ECM also regulates the cell differentiation and mineralization of tissues during craniofacial development. 31 Barreto et al (2017) 32 has shown that stiffer substrates can accelerate bone formation and suggested that ECM stiffness could lead to premature bone ossification in craniosynostosis, a condition characterized by the premature fusion of bones of the skull thus restricting brain growth and development. Aberrations in WNT signalling have also been reported in craniosynostosis, 33–35 while WNT2 was found to be dysregulated in Apert syndrome, a genetic condition characterized by fusion of the skull, hands, and feet bones.…”

SLIT3: a Novel Regulator of Odontogenic Differentiation through Akt/Wnt/β-catenin Signaling Pathway

“…As structural proteins, extracellular matrix proteins can regulate the activities of growth factors and proteases by interacting with receptors and integrins on the cell membrane 25 , which plays an important role in dentin formation and mineralization. Extracellular matrix protein SLIT3 initially entered the vision of researchers as guidance for axonal development 26 .…”

BRD4 binds to active cranial neural crest enhancers to regulate RUNX2 activity during osteoblast differentiation

“…) that regulate appropriate craniofacial development(Cruz Walma and Yamada 2022;Hatch 2010;Nakashima et al 2002). Other reports on CdLS related function have implicated a lack of BRD4 transcriptional effects as causative for the disorder.…”