A sex-specific switch in a single glial cell patterns the apical extracellular matrix

Area of Science:

• Cell biology
• Developmental biology
• Extracellular matrix research

Background:

• The apical extracellular matrix (aECM) forms a critical interface between tissues and their environment.
• The mechanisms by which aECM is patterned into diverse, tissue-specific structures remain largely unknown.

Purpose of the Study:

• To investigate the cellular and genetic basis for aECM patterning.
• To understand how a single cell can influence the structure of the surrounding extracellular matrix.

Main Methods:

• Utilized genetic screens in C. elegans to identify key regulatory genes.
• Employed cell-specific genetic sex reversal to determine cell-autonomous sex differences.
• Applied electron microscopy to visualize aECM structure and pore formation.
• Investigated the role of the Hedgehog-related protein GRL-18.

Main Results:

• A male-specific genetic switch in a glial cell transforms a solid aECM into a pore, enabling sensory neuron access.
• This glial sex difference is intrinsic and independent of neuronal sex identity.
• Identified shared (mab-3, lep-2, lep-5) and potentially glia-specific (nfya-1, bed-3, jmjd-3.1) regulators.
• Male-specific glial expression of GRL-18 is crucial for pore formation, localizing to nanoscale rings.

Conclusions:

• A single cell's gene expression switch is sufficient to pattern the apical extracellular matrix.
• The aECM is not uniform but possesses discrete, cell-identity-dependent local features.
• This study reveals a novel mechanism for how cellular identity dictates extracellular structure.