Organizer formation in Hydra is disrupted by thalidomide treatment

Abstract

Thalidomide is a drug that is well known for its teratogenic properties in humans. Surprisingly, thalidomide does not have teratogenic effects on mouse development. We investigated the effect of thalidomide on patterning in hydra, an early metazoan with a very simple axial symmetry. Hydra develops asexually via Wnt-dependent organizer formation, leading to the budding of a new organism. We observe both induction and inhibition of organizer formation depending on cellular context. Interestingly, thalidomide treatment altered budding and the developing organizer, but had little effect on the adult. Expression of Hybra1, a marker of the organizer increased upon thalidomide treatment. However when the organizer is induced by ectopic activation of Wnt signaling via GSK3 inhibition, thalidomide suppresses induction. We show that inhibition of Wnt signaling is not mediated by induction of the BMP pathway. We show that thalidomide activity on organizer formation in hydra depends on the activity of casein kinase1 and the abundance of β-catenin. Finally, we find that interstitial cells, multipotent cells which give rise to nemoatocytes, neural, digestive and germline cells, are partially responsible for the inhibitory effect of thalidomide.

Ancestral role of Fat-like cadherins in planar cell polarity

“…Visualization was done by ECL detection (Thermo Scientific). Whole mount immunofluorescence on Hydra polyps was done as described previously [48]. Primary antibodies dilutions were as follows: anti-HyFat total serum, 1:1500; affinity purified anti-HyFat ,1:100; anti-HyDs total serum, 1:400.…”

Thalidomide Embryopathy: An Enigmatic Challenge

“…It is well known that thalidomide exhibits species-specific differences in its teratogenic actions [1,3,8,129]. Many animal organisms have been used to study thalidomide's actions, including chicks, rabbits, zebrafish, marine fish, armadillos, marsupials, hydra, and nonhuman primates [1,2,44,54,121,123,159,[162][163][164][165]. One of the surprising aspects of thalidomide is that rodent embryos are less sensitive to thalidomide with varying results of activity as well as being mouse strain specific [166] and as such customarily are not seen as a primary tool to study thalidomide induced teratogenesis [165,[167][168][169][170][171][172][173][174].…”

The transcription factor Zic4 promotes tentacle formation and prevents epithelial transdifferentiation in Hydra

“…The fact that ectopic basal disc tissue can also develop at any place along the body column, mostly when Sp5 or Zic4 and Sp5 are knocked down, indicates that different constraints apply on the epithelial differentiation programs, with BDC differentiating in many places along the body axis and TBC differentiating only in tentacles. Several studies reported tentacle inhibition in Hydra (9,10,12,13,15); however, ectopic basal disc formation was never noticed in these contexts, suggesting that the transient genetic perturbations leading to tentacle inhibition were downstream of Zic4 and/or Sp5 activity, thus keeping active the Zic4-dependent repression of BDC differentiation.…”