Integrinα5 and Delta/Notch Signaling Have Complementary Spatiotemporal Requirements during Zebrafish Somitogenesis

Abstract

Somitogenesis is the process by which the segmented precursors of the skeletal muscle and vertebral column are generated during vertebrate embryogenesis. While somitogenesis appears to be a serially homologous, reiterative process, we find that there are differences between the genetic control of early/anterior and late/posterior somitogenesis. We demonstrate that point mutations can cause segmentation defects in either the anterior, middle, or posterior somites in the zebrafish. We find that mutations in zebrafish integrinalpha5 disrupt anterior somite formation, giving a phenotype complementary to the posterior defects seen in the notch pathway mutants after eight/deltaD and deadly seven/notch1a. Double mutants between the notch pathway and integrinalpha5 display somite defects along the entire body axis, with a complete loss of the mesenchymal-to-epithelial transition and Fibronectin matrix assembly in the posterior. Our data suggest that notch- and integrinalpha5-dependent cell polarization and Fibronectin matrix assembly occur concomitantly and interdependently during border morphogenesis.

Collective mesendoderm migration relies on an intrinsic directionality signal transmitted through cell contacts

“…In Xenopus, ECM and, in particular, fibronectin have been shown to play important roles in directing anterior mesoderm migration (39). A similar role for ECM in fish appears unlikely because the two fibronectin orthologues are not expressed on the track of the prechordal plate and the corresponding loss of functions, or integrin α5 loss of function, do not affect prechordal plate migration (40,41). Consistently, ECM (fibronectin and laminin) is first detected in the embryo at 65% epiboly, when the prechordal plate has already started its movement (42).…”

From segment to somite: Segmentation to epithelialization analyzed within quantitative frameworks

“…Fibronectin is found at chick (Duband et al, 1987) and zebrafish (Crawford et al, 2003) somite boundaries; in the latter case their accumulation is dependent on integrinalpha5 (Julich et al, 2005;Koshida et al, 2005). In zebrafish embryos deficient for both fibronectin and integrinalpha5, somite boundaries are initially formed but are not maintained, suggesting their role in boundary maintenance (Koshida et al, 2005).…”

Cell behaviors associated with somite segmentation and rotation in Xenopus laevis

“…However, it is known that anterior somites, also known as cranial somites, are somewhat smaller than later stage somites and that they degenerate by the onset of metamorphosis. In addition, it has recently been found in zebrafish that different molecular signaling processes govern the formation of anterior and posterior somites (Julich et al, 2005). Thus it is possible that different sets or subsets of cell behaviors are responsible for forming somites at the anterior and posterior ends of the X. laevis embryo.…”

“…Oates and Ha (2002) showed that, although the Delta/ Notch signaling pathway is required for the formation of somites along the entire axis, the formation of anterior somites also requires the activity of her 7, a downstream target of the Notch signaling pathway. In addition, it has been shown that integrin ␣5 is required for the formation of anterior, but not posterior somites (Julich et al, 2005). How these molecular differences translate into the patterning and functional differences among somites remains unclear.…”