title: A Sawtooth Pattern of Cadherin 2 Stability Mechanically Regulates Somite Morphogenesis.
abstract: Differential cadherin (Cdh) expression is a classical mechanism for in vitro cell sorting. Studies have explored the roles of differential Cdh levels in cell aggregates and during vertebrate gastrulation, but the role of differential Cdh activity in forming in vivo tissue boundaries and boundary extracellular matrix (ECM) is unclear. Here, we examine the interactions between cell-cell and cell-ECM adhesion during somitogenesis, the formation of the segmented embryonic precursors of the vertebral column and musculature. We identify a sawtooth pattern of stable Cdh2 adhesions in which there is a posterior-to-anterior gradient of stable Cdh2 within each somite, while there is a step-like drop in stable Cdh2 along the somite boundary. Moreover, we find that the posterior somite boundary cells with high levels of stable Cdh2 have the most columnar morphology. Cdh2 is required for maximal cell aspect ratio and thus full epithelialization of the posterior somite. Loss-of-function analysis also indicates that Cdh2 acts with the fibronectin (FN) receptor integrin α5 (Itgα5) to promote somite boundary formation. Using genetic mosaics, we demonstrate that differential Cdh2 levels are sufficient to induce boundary formation, Itgα5 activation, and FN matrix assembly in the paraxial mesoderm. Elevated cytoskeletal contractility is sufficient to replace differential Cdh2 levels in genetic mosaics, suggesting that Cdh2 promotes ECM assembly by increasing cytoskeletal and tissue stiffness along the posterior somite boundary. Throughout somitogenesis, Cdh2 promotes ECM assembly along tissue boundaries and inhibits ECM assembly in the tissue mesenchyme.
authors: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors: Patrick
authors: P
authors: McMillen
authors: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors: Veena
authors: V
authors: Chatti
authors: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors: Dörthe
authors: D
authors: Jülich
authors: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA. Electronic address: scott.holley@yale.edu.
authors: Scott A
authors: SA
authors: Holley
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D009024:Morphogenesis; D019170:Somites / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D015820:Cadherins; C513786:N-cadherin, zebrafish; D029961:Zebrafish Proteins
keywords: EphA4; boundary formation; cadherin 2; cytoskeletal contractility; differential adhesion; ephrinB2a; fibronectin; integrin α5; morphogenesis; segmentation; somite; zebrafish