Anchor Cell Invasion into the Vulval Epithelium in C. elegans

Abstract

An understanding of cell-invasive behavior has been limited by the lack of in vivo models where this activity can be clearly visualized and manipulated. We show that a single cell in the Caenorhabditis elegans gonad, the anchor cell (AC), initiates uterine-vulval contact through a cell invasion event. Using genetic analysis, laser ablations, and cell-specific markers, we demonstrate that AC invasion is predominantly stimulated by the 1 degrees vulval lineage cells, which generate a diffusible signal that promotes AC invasive behavior toward these cells and further targets invasive processes between the two central 1 degrees vulval lineage cells. We also show that AC invasion is regulated by the AC response to this cue, as well as a vulval-independent mechanism that weakly drives invasion. These studies dissect the regulatory mechanisms that underlie a simple cell-invasive behavior in vivo, and introduce AC invasion as a model for understanding key checkpoints controlling cell invasion.

LIN-12/Notch Regulates lag-1 and lin-12 Expression during Anchor Cell/Ventral Uterine Precursor Cell Fate Specification

“…The AC also invades the vulval epithelium during the VPC proliferation period (Sherwood and Sternberg, 2003). After the AC has induced the proliferation of VPCs and invaded the vulval epithelium, it fuses with some of the VU descendents to form an H-shaped structure (utse) in which component nuclei on both sides are connected by a thin laminar cytoplasmic bridge that separates the upper uterine and lower vulval lumens .…”

“…Vulval induction, AC invasion, and vulva-uterine connection analysis Vulval induction, anchor cell invasion, and vulval uterine connection were assayed as described previously (Hill and Sternberg, 1992;Hwang et al, 2007;Sherwood and Sternberg, 2003). In a wild-type hermaphrodite, three of the six VPCs adopt 1° and 2° cell fates to divide into 22 descendents during L3, which was measured in the transgenic lines expressing lag-1 cDNA in the AC from the AC-specific cdh-3 promoter (Kirouac and Sternberg, 2003).…”

“…AC invasion was measured at mid-L3 and the L3 molt using Nomarski optics. In wild-type animals, the basement membranes are degraded beneath the AC, and the basolateral side of the AC crosses through a hole in the basement membranes and penetrates between central 1°-fated vulval cells beginning in mid-L3, resulting in the overlap of AC cytoplasm with that of the vulval cells at early L4 (Sherwood and Sternberg, 2003). The ventral uterine cells form the connection between uterus and vulva through which eggs pass to exit the worm.…”

“…The VU cells undergo four rounds of cell division (Kimble and Hirsh, 1979;, whereas the AC remains a single cell in the gonad and expresses LIN-3, a member of the epidermal growth factor (EGF) family, that induces patterned proliferation of vulval precursor cells (VPCs) (Hill and Sternberg, 1992). The AC also invades the vulval epithelium by extending a process toward the 1° lineage (P6.p) of vulval cells (Sherwood and Sternberg, 2003). fos-1, a C. elegans homolog of the proto-oncogene Fos, is involved in the destruction of the underlying basement membranes during AC invasion (Sherwood et al, 2005).…”

Role of the extracellular matrix in epithelial morphogenesis

“…1). 13- 16 These events have been recently reviewed, 17 and Figure 1. Integrin contribution to BM invasion by the anchor cell (AC).…”