Microglia regulate GABAergic neurogenesis in prenatal human brain through IGF1

Area of Science:

• Neuroscience
• Developmental Biology
• Immunology

Background:

• GABAergic neurons are vital for neural circuits and human cognitive abilities.
• The expansion of GABAergic neurons in the human brain is significant but poorly understood.
• Understanding their developmental mechanisms is key to comprehending human brain evolution.

Purpose of the Study:

• To investigate the role of microglia in the development of GABAergic neurons in the human brain.
• To identify specific molecular mechanisms mediating microglia-progenitor communication.
• To elucidate how these interactions contribute to the increased number of GABAergic neurons in humans.

Main Methods:

• Single-cell transcriptomics and bioinformatics analyses were employed.
• Histological analyses were performed on prenatal human brain samples.
• Novel neuroimmune human medial ganglionic eminence (hMGE) organoids were developed and utilized.

Main Results:

• Microglia were identified as key regulators of GABAergic progenitor proliferation.
• Insulin-like growth factor 1 (IGF1) and its receptor IGF1R were found to be the primary communication signals.
• Microglia-derived IGF1 was shown to enhance progenitor proliferation and GABAergic neuron production in organoid models.

Conclusions:

• Microglia play a critical, previously unrecognized role in human GABAergic neuron development.
• Microglia-derived IGF1 is essential for sustaining the proliferation of neural progenitors.
• This mechanism contributes to the expanded production of GABAergic neurons in the human brain.