A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Transcriptional control is vital for neural connectivity, but specific transcription factor roles in axon guidance are unclear.
• Projection neurons in the dorsal spinal cord exhibit diverse axonal trajectories (ipsilateral vs. contralateral).

Purpose of the Study:

• To investigate the role of LIM homeodomain proteins Lhx2 and Lhx9 in the axon guidance of specific commissural relay neurons (dI1c neurons).

Main Methods:

• Utilized Lhx2/9 double mutant mice to assess axon projection defects.
• Examined the expression of Rig-1 in dI1c neurons.
• Investigated Lhx2 binding to the Rig-1 gene promoter.

Main Results:

• Lhx2 and Lhx9 are expressed in dI1c neurons and are essential for their axon projection.
• Lhx2/9 double mutants exhibit a complete loss of dI1c axon midline crossing.
• This defect is linked to the downregulation of Rig-1 expression in dI1c axons.
• Lhx2 directly binds to a conserved motif in the Rig-1 gene.

Conclusions:

• Lhx2/9 transcription factors directly regulate Rig-1 expression, controlling a critical step in dI1c axon guidance.
• Establishes a link between transcriptional programs defining neuronal identity and axon guidance receptor expression.