Evolution and Developmental System Drift in the Endoderm Gene Regulatory Network of Caenorhabditis and Other Nematodes

Abstract

Developmental gene regulatory networks (GRNs) underpin metazoan embryogenesis and have undergone substantial modification to generate the tremendous variety of animal forms present on Earth today. The nematode Caenorhabditis elegans has been a central model for advancing many important discoveries in fundamental mechanistic biology and, more recently, has provided a strong base from which to explore the evolutionary diversification of GRN architecture and developmental processes in other species. In this short review, we will focus on evolutionary diversification of the GRN for the most ancient of the embryonic germ layers, the endoderm. Early embryogenesis diverges considerably across the phylum Nematoda. Notably, while some species deploy regulative development, more derived species, such as C. elegans, exhibit largely mosaic modes of embryogenesis. Despite the relatively similar morphology of the nematode gut across species, widespread variation has been observed in the signaling inputs that initiate the endoderm GRN, an exemplar of developmental system drift (DSD). We will explore how genetic variation in the endoderm GRN helps to drive DSD at both inter- and intraspecies levels, thereby resulting in a robust developmental system. Comparative studies using divergent nematodes promise to unveil the genetic mechanisms controlling developmental plasticity and provide a paradigm for the principles governing evolutionary modification of an embryonic GRN.

Keywords: Caenorhabditis; developmental hourglass; developmental system drift; plasticity; robustness.

FIGURE 1

Caenorhabditis elegans founder cells and the endoderm specification network. Asymmetrical cell divisions produce six founder cells, each of which will give rise to specific tissue types. At the four-cell stage, SKN-1 activates the med-1,2 genes, initiating mesendoderm specification. Redundant Wnt/MAPK/Src signaling arising from the neighboring P₂ cell polarizes EMS. In the anterior, un-signaled end, POP-1 represses end-1 and end-3 expression while MED-1,2 turn on tbx-35, which in turn specify mesoderm MS fate. In the posterior end, LIT-1 kinase, in response to P₂ signals, phosphorylates POP-1 (indicated by *), converting it from a repressor to an activator of endoderm E fate. The two differentiation factors, ELT-7 and ELT-2, once activated, maintain their own expression through autoregulation and regulate thousands of gut genes. In E, Wnt signaling further represses tbx-35 expression (Broitman-Maduro et al., 2006).

FIGURE 2

Variation in early embryogenesis in Nematoda. Nematodes are classified into 12 clades based on rDNA sequence (Holterman et al., 2006). Basal Tobrillus undergoes a “canonical” protostome-like gastrulation characterized by invagination of eight endoderm precursors (red nuclei) at the anterior blastopore during 64 cell-stage. Gastrulation in more highly derived nematodes is driven by apical constriction of endoderm precursors at the postero-ventral surface of 28 cell-stage embryo (adapted from Joshi and Rothman, 2005). Unlike species in the early branching clades, in which cell fates are plastic and rely on external signals (“regulative” development), cell lineages are largely fixed during early division (“mosaic development”) in more derived species. In addition, developmental rate is faster in the more derived clades. Thus, it is proposed that heterochronic and heterotopic shift in the developmental program drive the evolution of early embryogenesis in nematodes.