The zebrafish masterblind (mbl) mutation reduces the activity of Axin1, a negative regulator of the Wnt/β-catenin signalling pathway. Kapsimali et al. found that in mbl embryos the floor plate was expanded at the expense of hypothalamic tissue. However, the hypothalamic domain could be restored by transplanting axin1-overexpressing epiblast cells into the prospective floor plate of young mbl embryos. Transplantation of these same cells into the prospective floor plate of wild-type embryos induced ectopic expression of hypothalamic marker genes at midbrain and hindbrain levels. Together, these observations indicate that induction of hypothalamic tissue at the ventral midline requires inhibition of the Wnt/β-catenin pathway.
Intriguingly, not all Wnt inhibitors seem to be equally capable of promoting hypothalamic fate. The authors tested the effects of various intracellular and extracellular Wnt antagonists, and found that the intracellular antagonists, which included Axin1, induced ectopic expression of hypothalamic markers in the ventral CNS, whereas secreted inhibitors, such as Dickkopf1, Tlc and the frizzled-related protein Frzb1, did not. So, what other properties of the intracellular Wnt inhibitors might underlie their ability to induce hypothalamic tissue? One possible explanation comes from the finding that Axin1 seems to facilitate Nodal signalling — a pathway that is known to be required for the development of the floor plate and ventral hypothalamus. The authors found that both Nodal pathway activation and Axin1 expression promoted the insertion of cells into the ventral midline.
This is a preview of subscription content, access via your institution
