Sequential requirement of Sox4 and Sox11 during development of the sympathetic nervous system

Area of Science:

• Developmental biology
• Neuroscience
• Genetics

Background:

• The transcription factors Sox4 and Sox11 (SoxC proteins) are expressed in the developing sympathetic nervous system.
• Their specific roles in this tissue are not fully understood, particularly in contrast to their known functions in central nervous system neuronal precursors.

Purpose of the Study:

• To investigate the distinct and overlapping functions of Sox4 and Sox11 in the development of the sympathetic nervous system.
• To elucidate the molecular mechanisms by which these transcription factors regulate sympathetic neuron development.

Main Methods:

• Mouse mutagenesis to create genetic loss-of-function models for Sox4 and Sox11.
• Overexpression studies in chicken embryos to assess functional roles.
• Analysis of sympathetic ganglia development, cell proliferation, survival, and differentiation markers.

Main Results:

• Sox4 and Sox11 do not primarily drive pan-neuronal or noradrenergic differentiation in sympathetic neurons.
• Sox11 is essential for the proliferation of tyrosine hydroxylase-expressing cells in early sympathetic ganglia.
• Sox4 is required for the survival of these cells at later developmental stages.
• Combined loss of Sox4 and Sox11 leads to hypoplastic sympathetic ganglia due to consecutive proliferation and survival defects.

Conclusions:

• Sox4 and Sox11 play distinct, sequential roles in sympathetic nervous system development: Sox11 for proliferation and Sox4 for survival.
• Disruption of these functions results in rudimentary sympathetic ganglia, impaired innervation, and severe dysautonomia.
• These findings highlight a unique role for SoxC proteins in the peripheral nervous system development, distinct from their CNS functions.