Initiation of convergence and extension movements of lateral mesoderm during zebrafish gastrulation

Abstract

Embryonic morphogenesis is accomplished by cellular movements, rearrangements, and cell fate inductions. Vertebrate gastrulation entails morphogenetic processes that generate three germ layers, endoderm, mesoderm, and ectoderm, shaped into head, trunk, and tail. To understand how cell migration mechanistically contributes to tissue shaping during gastrulation, we examined migration of lateral mesoderm in the zebrafish. Our results illustrate that cell behaviors, different from mediolaterally oriented cell intercalation, also promote convergence and extension (C&E). During early gastrulation, upon internalization, individually migrating mesendodermal cells contribute to the elongation of the mesoderm by moving animally, without dorsal movement. Convergence toward dorsal starts later, by 70% epiboly (7.7 hpf). Depending on location along the Animal-Vegetal axis, an animal or vegetal bias is added to the dorsalward movement, so that paths fan out and the lateral mesoderm both converges and extends. Onset of convergence is independent of noncanonical Wnt signaling but is delayed when Stat3 signaling is compromised. To understand which aspects of motility are controlled by guidance cues, we measured turning behavior of lateral mesodermal cells. We show that cells exhibit directional preference, directionally-regulated speed, and turn toward dorsal when off-course. We estimate that ectoderm could supply from a fraction to all the dorsalward displacement seen in mesoderm cells. Using mathematical modeling, we demonstrate that directional preference is sufficient to account for mesoderm convergence and extension, and that, at minimum, two sources of guidance cues could orient cell paths realistically if located in the dorsal midline. Developmental Dynamics 234:279 -292, 2005.

Mesodermal cell displacements during avian gastrulation are due to both individual cell-autonomous and convective tissue movements

“…For example, Sepich et al (6) tracked the motion of gastrulating mesodermal cells in zebrafish, as well as cells in the ectoderm, and assumed that some (arbitrary) percentage of shared motion between different layers represented passive cell convection. Their approach to separating active cell displacements from the ''background'' motion of tissue morphogenesis is inherently limited because the analysis had no fixed frame of reference (''ground'') for relating the total cell motion.…”

“…One of the most challenging problems in studying the dynamics of cell displacements during gastrulation is separating local (individual) cell-autonomous motility from large-scale (convective) tissue-level morphogenetic displacements (5,6), which added together account for total mesodermal cell displacement (operational definitions for these terms are given in Materials and Methods).…”

Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm

“…Sepich et al (2005) showed that after 70% epiboly, the directional movement of central and vegetal lateral mesoderm cells toward the dorsal aspect is sufficient to account for mesodermal convergence and extension of the presomitic mesoderm and that these movements are independent of the ectoderm. Our rescue experiments showed that a balance of p120 catenin d1 and Cdc42, and Rac1 and RhoA GTPases is required for normal convergence and extension.…”

“…During gastrulation, presumptive mesodermal cells internalize beneath the ectodermal cells and migrate toward the dorsal axis to become the notochord and the presomitic mesoderm (Keller et al, 2000;Yin et al, 2009). Convergence and extension movements accompanying this migration cause mediolateral narrowing and antero-posterior lengthening of the dorsal axis of the zebrafish embryo (Warga and Kimmel, 1990;Sepich et al, 2005). However, little is known regarding the roles of p120 catenin d1 (p120 catenin in other vertebrates), Rac1, or Cdc42 GTPases in zebrafish development (Bakkers et al, 2004;Wildenberg et al, 2006).…”

Analysis of axis induction mutant embryos reveals morphogenetic events associated with zebrafish yolk extension formation

“…Convergence and extension movements begin shortly after the initiation of gastrulation (6 hpf). Convergence involves the migration of polarized cells toward the dorsal side (Warga and Kimmel, 1990;Jensen et al, 2002), leading to the accumulation of cells in this region and the thickening of the dorsal axis, whereas extension, and thus elongation, occurs by a combination of directed migration (Glickman et al, 2003) and the intercalation of neighboring cells in the dorsal region (Sepich et al, 2005).…”