Afadin sorts different retinal neuron types into accurate cellular layers.

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Cell-adhesion molecules (CAMs) mediate neuronal interactions, influencing migration, morphology, and synaptic connections.
• The intracellular signaling pathways downstream of CAMs, particularly in different neuron types, remain poorly understood.

Purpose of the Study:

• To investigate the role of Afadin, a cytosolic adapter protein linking CAMs to F-actin, in neural development.
• To elucidate Afadin's function in retinal neuron organization and visual processing using a conditional mouse mutant.

Main Methods:

• Utilized a conditional Afadin mouse mutant crossed with a retinal Cre driver (Six3Cre).
• Employed viral labeling and genetic manipulation to analyze retinal neuron distribution and function.
• Assessed neuron fate specification, survival, synaptic connections, and visual function in mutant mice.

Main Results:

• Afadin deficiency in retinal neurons caused scrambled distribution of bipolar cells, amacrine cells, and retinal ganglion cells across retinal layers.
• Mutant neurons showed normal fate specification and survival, with preserved RGC-AC synaptic partnering.
• Significant visual function decline and mis-targeting of RGC axons to the superior colliculus were observed.

Conclusions:

• Afadin plays a critical role in the precise lamination of retinal neurons, establishing the structural basis for visual processing.
• Afadin's function in neuron sorting is distinct from its role in specifying cell fate or survival.
• Disruption of Afadin-mediated sorting leads to impaired visual function and aberrant axonal projections.