Balancing SHH and BMP/FGF10 to specify tuberal hypothalamic neurons and glia

The tuberal hypothalamus harbours clinically important neuronal and glial populations with central roles in energy homeostasis. Previous work has revealed key roles for SHH and BMP signalling in tuberal progenitor specification, and suggested that dynamic BMP signalling specifies tuberal hypothalamic progenitors from hypothalamic floor plate-like (HypFP) cells in an anterior (neurogenic) to posterior (gliogenic) sequence. Here, through gain- and loss-of-function studies in vivo and ex vivo, we provide evidence that FGF10, which is induced by BMP signalling, operates with SHH and BMP to contribute to neurogenic and gliogenic fates. Our results indicate that SHH levels must be finely-tuned to support sustained tuberal neurogenesis, and are consistent with a model in which transient BMP/FGF10 signalling activity in anterior-most HypFP cells reduces SHH expression, in a manner that optimises tuberal neurogenic specification rate during a critical developmental period, while sustained BMP/FGF10 signalling activity in mid-HypFP cells promotes tuberal gliogenic fate.