The Molecular Basis of Organ Formation: Insights From theC. elegansForegut

Abstract

The digestive tracts of many animals are epithelial tubes with specialized compartments to break down food, remove wastes, combat infection, and signal nutrient availability. C. elegans possesses a linear, epithelial gut tube with foregut, midgut, and hindgut sections. The simple anatomy belies the developmental complexity that is involved in forming the gut from a pool of heterogeneous precursor cells. Here, I focus on the processes that specify cell fates and control morphogenesis within the embryonic foregut (pharynx) and the developmental roles of the pharynx after birth. Maternally donated factors in the pregastrula embryo converge on pha-4, a FoxA transcription factor that specifies organ identity for pharyngeal precursors. Positive feedback loops between PHA-4 and other transcription factors ensure commitment to pharyngeal fate. Binding-site affinity of PHA-4 for its target promoters contributes to the progression of the pharyngeal precursors towards differentiation. During morphogenesis, the pharyngeal precursors form an epithelial tube in a process that is independent of cadherins, catenins, and integrins but requires the kinesin zen-4/MKLP1. After birth, the pharynx and/or pha-4 are involved in repelling pathogens and controlling aging.

The Conserved miR-51 microRNA Family Is Redundantly Required for Embryonic Development and Pharynx Attachment in Caenorhabditis elegans

“…Early morphogenesis of the pharynx occurs in several phases (Sulston et al 1983;Portereiko and Mango 2001;Mango 2009). In the first phase, the lumen of the pharynx elongates through polarization of the anterior pharyngeal cells ( Figure 3A).…”

“…At this point, the nuclei of the arcade cells have been displaced posteriorly but remain attached to the arcade ring through cytoplasmic bridges ( Figure 3A, bottom). Genetic analyses have identified Pun mutants that fail at different times during buccal morphogenesis (Portereiko and Mango 2001;Mango 2009). To check for polarization of the anterior pharyngeal cells in our mutants, we visualized adherens junctions through staining of embryos with an a-MH27 antibody, which recognizes AJM-1 (Figure 3, B-G).…”

Laminin is required to orient epithelial polarity in theC. eleganspharynx

“…Because the transcription factor PHA-4 (FoxA) is thought to be required for most, if not all, aspects of pharyngeal-specific differentiation (reviewed by Mango, 2009), we examined formation of the double plate in pha-4(q490) null mutants. We found that the timing and patterning of the early PPC divisions in pha-4(q490) embryos appeared similar to wild type (data not shown) and that all of the PPCs ingressed (Fig.…”

A Regulatory Module Controlling Pharyngeal Development and Function in Caenorhabditis elegans

“…In Caenorhabditis elegans, the foregut, which includes the buccal cavity, pharynx, and intestinal valve cells, has proven to be a powerful model for studies of the molecular mechanisms controlling organogenesis (Mango 2007(Mango , 2009. Although containing only 95 nuclei in the adult, the foregut is composed of seven distinct but functionally integrated cell types, which arise from diverse embryonic lineages (Albertson and Thomson 1976;Sulston et al 1983).…”