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

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• The tuberal hypothalamus contains vital neuronal and glial cells regulating energy homeostasis.
• Sonic hedgehog (SHH) and bone morphogenetic protein (BMP) signaling are known to be key in tuberal progenitor specification.
• Previous studies suggested dynamic BMP signaling drives tuberal hypothalamic progenitor specification sequentially from anterior to posterior.

Purpose of the Study:

• To investigate the role of FGF10, induced by BMP signaling, in tuberal hypothalamus development.
• To elucidate the interplay between SHH, BMP, and FGF10 in neurogenic and gliogenic fates.
• To understand the precise regulation of SHH levels for neurogenesis and gliogenesis.

Main Methods:

• In vivo and ex vivo gain- and loss-of-function studies.
• Analysis of signaling pathways including SHH, BMP, and FGF10.
• Investigation of progenitor specification in the tuberal hypothalamus.

Main Results:

• FGF10, induced by BMP signaling, collaborates with SHH and BMP to influence neurogenic and gliogenic outcomes.
• Optimal tuberal neurogenesis requires finely-tuned SHH levels.
• Transient BMP/FGF10 signaling in anterior cells reduces SHH, optimizing neurogenesis; sustained signaling in mid-HypFP cells promotes gliogenesis.

Conclusions:

• FGF10 is a critical factor, alongside SHH and BMP, in specifying tuberal hypothalamic neuronal and glial fates.
• SHH levels must be precisely regulated to balance neurogenesis and gliogenesis during development.
• A model is proposed where transient vs. sustained BMP/FGF10 signaling differentially regulates SHH to control neurogenic and gliogenic rates.