A Krüppel-like factor is required for development and regeneration of germline and yolk cells from somatic stem cells in planarians

Abstract

Sexually reproducing animals segregate their germline from their soma. In addition to gamete-producing gonads, planarian and parasitic flatworm reproduction relies on yolk cell–generating accessory reproductive organs (vitellaria) supporting development of yolkless oocytes. Despite the importance of vitellaria for flatworm reproduction (and parasite transmission), little is known about this unique evolutionary innovation. Here, we examine reproductive system development in the planarian Schmidtea mediterranea, in which pluripotent stem cells generate both somatic and germ cell lineages. We show that a homolog of the pluripotency factor Klf4 is expressed in primordial germ cells (PGCs), presumptive germline stem cells (GSCs), and yolk cell progenitors. Knockdown of this klf4-like (klf4l) gene results in animals that fail to specify or maintain germ cells; surprisingly, they also fail to maintain yolk cells. We find that yolk cells display germ cell–like attributes and that vitellaria are structurally analogous to gonads. In addition to identifying a new proliferative cell population in planarians (yolk cell progenitors) and defining its niche, our work provides evidence supporting the hypothesis that flatworm germ cells and yolk cells share a common evolutionary origin.

Probing the evolutionary dynamics of whole-body regeneration within planarian flatworms

“…To explore putative Wnt signalling functions in the planarian RS, we turned to the sexual laboratory strain of the model species Smed. The RS in adults of this strain 64,65 (Fig. 5c) can be collectively ablated through the knockdown of the orphan G-protein coupled receptor ophis 66 .…”

Planarians to schistosomes: an overview of flatworm cell-types and regulators

“…Pioneering work from the Newmark laboratory and others first identified nanos , an RNA-binding protein with a crucial role in germ cell development across metazoan (Seydoux & Braun, 2006), to be expressed in presumptive male and female germline stem cells (GSCs), and plays an essential role in germ cell specification and maintenance (Sato et al , 2006; Wang et al , 2007, 2010). Recently, a Krüppel-like factor associated with pluripotency (Takahashi & Yamanaka, 2006), klf4-like ( klfl ), was found to be expressed in the earliest stage of germ cell development (Issigonis et al , 2022; Khan & Newmark, 2022). klfl is largely co-expressed with nanos in the earliest male and female GSCs as well as in vitellaria and is essential for the specification and maintenance of germ cells and yolk cells (Issigonis et al , 2022).…”

“…Recently, a Krüppel-like factor associated with pluripotency (Takahashi & Yamanaka, 2006), klf4-like ( klfl ), was found to be expressed in the earliest stage of germ cell development (Issigonis et al , 2022; Khan & Newmark, 2022). klfl is largely co-expressed with nanos in the earliest male and female GSCs as well as in vitellaria and is essential for the specification and maintenance of germ cells and yolk cells (Issigonis et al , 2022). In addition to nanos and klfl , multiple factors have been identified to play a role in germ cell development and maintenance.…”

A niche-derived non-ribosomal peptide triggers planarian sexual development

“…S4B). We examined the effects of nrps knockdown on female reproductive development by double FISH to detect the germline stem cell marker klf4l (17) with early germ cell marker nanos (17,(20)(21)(22)(23) or somatic niche marker ophis. nrps RNAi resulted in a significant reduction or complete loss of klf4l + nanos + germ cells in the anterior ovarian fields located mediolaterally along the brain and within the ovaries themselves.…”