Cadherins in early neural development

Abstract

During early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

Sildenafil as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons

“…It has a critical role in tau aggregation [ 48 ]. Cadherin regulates complex signaling cascades including amyloid-β protein precursor (APP), vascular endothelial growth factor (VEGF), morphogenesis, plasticity, Wnt-mediated signaling, etc., in neurodegenerative disorders [ 49 ]. These have important role for synaptic loss and decline in synaptic plasticity [ 50 ].…”

APOE3 Christchurch modulates β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases

“…The effects of APOE3Ch on Wnt and Cadherin signaling uncovered by scRNA sequencing of cerebral organoids were unexpected and may operate via multiple mechanisms, ultimately resulting in β-catenin upregulation. Cadherins are a family of calcium-dependent transmembrane adhesion proteins that link β- and α-catenin to the actin cytoskeletal network ( Punovuori et al, 2021 ) and also regulate cellular homeostasis through signaling mediating development, proliferation, apoptosis, and disease pathology ( Yulis et al, 2018 ). Cadherins regulate calcium-dependent cell–cell adherent junctions, where the chelation of calcium abolishes adhesive activity and allows proteolytic degradation of cadherins ( Nagar and Overduint, 1996 ; Kim et al, 2011 ).…”

APOE3Christchurch modulates tau phosphorylation and β-catenin/Wnt/Cadherin signaling in induced pluripotent stem cell-derived cerebral organoids from Alzheimer’s cases

“…The effects of APOE3Ch on Wnt and Cadherin signaling uncovered by scRNA-sequencing of cerebral organoids were unexpected and may operate via multiple mechanisms ultimately resulting in β-catenin upregulation. Cadherins are a family of calcium dependent transmembrane adhesion proteins that link β and α catenin to the actin cytoskeletal network (Punovuori, Malaguti, and Lowell 2021) and also regulate cellular homeostasis through signaling mediating development, proliferation, apoptosis, and disease pathology (Yulis, Kusters, and Nusrat 2018). Cadherins regulate calcium dependent cell-cell adherent junctions, where the chelation of calcium abolishes adhesive activity and allows proteolytic degradation of cadherins (Nagar and Overduint 1996; Kim et al 2011).…”