A central role for Numb/Nbl in multiple Shh-mediated axon repulsion processes.

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Sonic hedgehog (Shh) is a key signaling molecule involved in axon guidance.
• Shh exhibits dual functions, acting as both a chemoattractant and a chemorepellent depending on context.
• The precise molecular mechanisms governing Shh's dual role, particularly in repulsion, remain incompletely understood.

Purpose of the Study:

• To investigate the role of the endocytic adaptor Numb in Shh-mediated axon guidance.
• To elucidate the molecular mechanisms underlying Shh's repulsive functions in different neural contexts.
• To determine if Numb is essential for Shh-mediated repulsion.

Main Methods:

• Utilized genetic models to study axon guidance in the developing spinal cord and visual system.
• Examined the function of Numb in Shh-mediated repulsion of commissural axons and retinal ganglion cell axons.
• Investigated the involvement of Numb in non-canonical Shh signaling pathways.

Main Results:

• Numb was found to be essential for Shh-mediated repulsion of ipsilateral retinal ganglion cell (iRGC) axons at the optic chiasm.
• Numb is also required for Shh-mediated antero-posterior commissural axon repulsion in the spinal cord.
• These findings demonstrate Numb's necessity for both Shh attraction and repulsion.

Conclusions:

• Numb plays a critical role in mediating Shh-driven axon repulsion.
• Numb is indispensable for Shh-mediated attraction and repulsion, underscoring its versatility.
• Numb is identified as a central component of the non-canonical Shh signaling pathway responsible for axon repulsion.