Development: birth, life, death, cleanup, repeat.
Original Research Article:
HH Wu, E Bellmunt, JL Scheib, V Venegas, C Burkert, LF Reichardt, Z Zhou, I Fariñas, BD Carter (2009). Glial precursors clear sensory neuron corpses during development via Jedi-1, an engulfment receptor. Nat Neurosci. 12 (12): 1534-1541.
The development of a nervous system entails several obvious processes such as the proliferation of cells, the elaboration of dendrites, or the wiring of functional axonal circuits, yet it is now becoming clear that the less publicized (and slightly more sinister) mechanisms of programmed cell death and debris clearance are a vital component of nervous growth. For example, in the mouse dorsal root ganglia (DRG) over 50% of sensory neurons undergo apoptosis during embryogenesis. The rapid and controlled clearance of these dead cells is vital, as non-ingested cells can generate inflammation and detrimental immune responses.
In a recent Nature Neuroscience article, a team led by Bruce Carter recognizes a specialized glial cell, satellite glial cell precursors (SGC), in the clearance of dead neurons in the dorsal root ganglia of embryonic mice. Previously, it was unclear which cells were responsible for apoptotic clearance, with default responsibility handed to macrophages. However, through confocal and electron microscopy and in vitro assays, the group demonstrates that the vast majority of apoptotic neurons are associated or engulfed within SGC’s, highlighting an unrecognized role for glial cells in phagocytosis.
In addition, the group provided a potential molecular mechanism for engulfment of dead cells. Jedi-1 and MEGF10, homologues of known c. elegans and Drosophila proteins, are expressed in the brain and specifically within SGCs in the DRG. Transient expression of the either protein in cultured HEK cells led to binding of neuronal corpses, and overexpression of the proteins in glial cells leads to increased engulfment of dead cells, suggesting a clear role for Jedi-1 and MEGF10 as engulfment receptors. Through their research, Wu et al establish satellite glial cell precursors as members of the ‘clean-up’ crew in the peripheral nervous system, performing a similar role as microglia in the brain, and importantly implicate two receptors as crucial sensors in the proper clearance of apoptotic cells.