Temperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways

Abstract

How multicellular organisms assess and control their size is a fundamental question in biology, yet the molecular and genetic mechanisms that control organ or organism size remain largely unsolved. The freshwater polyp Hydra demonstrates a high capacity to adapt its body size to different temperatures. Here we identify the molecular mechanisms controlling this phenotypic plasticity and show that temperature-induced cell number changes are controlled by Wnt- and TGF-β signaling. Further we show that insulin-like peptide receptor (INSR) and forkhead box protein O (FoxO) are important genetic drivers of size determination controlling the same developmental regulators. Thus, environmental and genetic factors directly affect developmental mechanisms in which cell number is the strongest determinant of body size. These findings identify the basic mechanisms as to how size is regulated on an organismic level and how phenotypic plasticity is integrated into conserved developmental pathways in an evolutionary informative model organism.

Bacteria- and temperature-regulated peptides modulate beta-catenin signaling inHydra

“…Animals reared at 18°C formed ~40% more ectopic tentacles than animals reared at 12°C (Figure 1B), indicating that temperature modulates Wnt-signaling and thus plays a role in controlling axis formation and maintenance of the proliferation zone in Hydra. These data are in agreement with earlier observations 50 . In order to proof that temperature is interfering with the Wnt-signaling pathway, we reared transgenic animals, carrying a constitutively active β -catenin overexpression (OE) 37 construct at 12°C and 18°C.…”

“…To investigate whether temperature interferes with the Wnt-dependent developmental program in Hydra we cultured polyps at 12 °C and 18 °C and treated the animals with Alsterpaullone (ALP) (Figure 1A). ALP is an inhibitor for GSK3-β and causes an activation of the Wnt-signaling pathway 42,50,51 .…”

“…To elucidate the underlying molecular mechanism of the environment-development interaction, we compared differentially regulated genes of a previous microarray study comparing GF to control animals 52 with a recent RNA-seq data set 50 , which compared the transcriptome of animals reared at 12°C and 18°C. Both sets of differentially regulated genes overlapped in 55 contigs ( Figure 3A, Table S1).…”

“…Hydra polyps change their body size under different rearing temperatures or feeding regimes 48,49 . We recently could show that temperature acts on the Wnt-TGF-β signaling axis, which influences the outcome of developmental decisions such as budding and thereby size regulation of the adult polyp 50 . Starvation leads to shrinking of the animals while overfeeding leads to morphological anomalies 49 .…”

Dynamic interactions within the host-associated microbiota cause tumor formation in the basal metazoan Hydra

“…The clonal culture of healthy H. oligactis demonstrates a very low interindividual variation, evident in minimal deviations in the number of tentacles ( Fig 3J), bud detachment time ( Fig 3L), mesoglea thickness (S5A Fig) and number of epithelial cells (S5B Fig). This is not surprising, since the number of tentacles and pattern of their emergence as well as the number of cells per polyp are species-specific traits and are genetically controlled [25][26][27]. In tumorous polyps, interindividual variation is markedly higher compared to the healthy polyps.…”