The microRNA pathway controls germ cell proliferation and differentiation in C. elegans

Abstract

The discovery of the miRNA pathway revealed a new layer of molecular control of biological processes. To uncover new functions of this gene regulatory pathway, we undertook the characterization of the two miRNA-specific Argonaute proteins in Caenorhabditis elegans, ALG-1 and ALG-2. We first observed that the loss-of-function of alg-1 and alg-2 genes resulted in reduced progeny number. An extensive analysis of the germline of these mutants revealed a reduced mitotic region, indicating fewer proliferating germ cells. We also observed an early entry into meiosis in alg-1 and alg-2 mutant animals. We detected ALG-1 and ALG-2 protein expressions in the distal tip cell (DTC), a specialized cell located at the tip of both C. elegans gonadal arms that regulates mitosis-meiosis transition. Re-establishing the expression of alg-1 specifically in the DTC of mutant animals partially rescued the observed germline defects. Further analyses also support the implication of the miRNA pathway in gametogenesis. Interestingly, we observed that disruption of five miRNAs expressed in the DTC led to similar phenotypes. Finally, gene expression analysis of alg-1 mutant gonads suggests that the miRNA pathway is involved in the regulation of different pathways important for germline proliferation and differentiation. Collectively, our data indicate that the miRNA pathway plays a crucial role in the control of germ cell biogenesis in C. elegans.

Functional analysis of microRNA pathway genes in the somatic gonad and germ cells during ovulation in C. elegans

“…The activation is required for resumption of meiosis in the proximal oocyte (Govindan et al, 2009). ALG-1 and ALG-2 together with a set of miRNAs expressed in the distal tip cell of the somatic gonad maintain germ cell proliferation, oocyte abundance and brood size (Bukhari et al, 2012). Therefore the decrease in ovulation rate and brood size that we observed following knock down of ALG-1 and ALG-2 in the somatic gonad may result from reduced miRNA activity in the distal tip cell.…”

“…These results indicate that miRNAs are required in the mouse somatic gonad for normal fertility. In worms, Dicer/ dcr-1 activity is required in the somatic gonad for fertility (Drake et al, 2014) and Argonaute/ alg-1 acts in the somatic distal tip cell to control germline proliferation (Bukhari et al, 2012). However, the specific events of oocyte maturation and ovulation that require miRNA activity in the somatic gonad cells in worms remain unknown.…”

Thyroid Hormone Analogue Stimulates Keratinocyte Proliferation but Inhibits Cell Differentiation in Epidermis

“…Our data illustrated that the level of differentiation markers Involucrin and Loricrin were decreased greatly, indicating that thyroid hormones have negative effect on cell differentiation. The balance between cell proliferation and differentiation is a key aspect of development in multicellular organisms (23)(24), including dermal thickening and wound healing. It is believed that there are many specific proteins that could induce cell differentiation.…”

The Use of the Nematode Caenorhabditis elegans to Evaluate the Adverse Effects of Epoxiconazole Exposure on Spermatogenesis

“…The age-matched L2-larvae nematodes were exposed to epoxiconazole for 12 h. Entry into meiosis was confirmed by looking at the first appearance of crescent-shaped nuclei in L3-larvae (12 h after L2) in the mitotic region/transition zone [31]. Ten nematodes were used to calculate the percentage of meiotic entry (meiotic entry worms/total worms × 100).…”