Figure 8.

Experimental model of visceral motor neuron loss in CCHS. Nkx2.2^Cre, Phox2b^Δ8 E10.5 embryos and controls were stained with antibodies against N‐terminal PHOX2B, NKX2.2 and ISLET1 (A‐E). Note the decrease in ISLET1‐positive motor neurons is noted in D1. E. Proposed model of visceral motor neuron maldevelopment. Wild‐type scenario is artistically rendered on left side, which illustrates a self‐renewing Nkx2.2 progenitor stage, giving rise to a Phox2b positive proliferative pool with transit amplifying characteristics, which then give rise to terminally differentiated ISELT1 positive cells. In CCHS, the proliferative PHOX2B population is reduced, and there is an expansion of the Nkx2.2 proliferative population, resulting over time to a net decreased production of ISLET1 positive cells.