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


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

Fig 8. Germ cell niche factor ophis is required to sustain yolk cell production/vitellogenesis.
(A–C) Maximum intensity projections of confocal sections showing FISH of LamA (A), klf4l (B), and MX1 (C) (green) in the ventral posterior region of sexually mature control versus ophis RNAi animals. Dashed line denotes planarian boundary. N = 3 to 5 experiments, n = 7 to 26 planarians. (A) ophis RNAi results in a dramatic loss of the LamA+ cells throughout the vitellaria. Note that LamA expression is only visible in the branched gut in ophis RNAi planarians. (B, C) ophis RNAi results in a reduction of klf4l+ yolk cell progenitors and MX1+ differentiated yolk cells. (A–C) Nuclei are counterstained with DAPI (gray). Scale bars, 200 μm. (D) Model depicting similarities shared between gonads (where gametogenesis occurs) and vitellaria (where yolk cell production occurs). klf4l+/nanos+/piwi-1+ presumptive GSCs in testes and ovaries divide and give rise to klf4l–/nanos+/piwi-1+ progeny. These germ cells are supported by ophis+ somatic gonadal niche cells. Vitellaria are comprised of klf4l+/nanos+/piwi-1+ “germ cell–like” yolk progenitors that are mitotically competent, sustain yolk cell production, and are supported by ophishigh support cells. FISH, fluorescent RNA in situ hybridization; klf4l, klf4-like; RNAi, RNA interference.


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.

Melanie Issigonis, Akshada B Redkar, Tania Rozario, Umair W Khan, Rosa Mejia-Sanchez, Sylvain W Lapan, Peter W Reddien, Phillip A Newmark. PLoS Biol. 2022 Jul 15;20(7):e3001472. doi: 10.1371/journal.pbio.3001472.