Table 1.

The cell of origin and known heterotypic interactions in multiple NF1 symptoms

Neoplasia	Cell of origin	Other cells
Plexiform neurofibromas	Nf1^-/- Schwann cells or their precursors	Nf1^+/- mast cells
CNS gliomas	Nf1^-/- astrocytes	Nf1^+/- microglia
Dermal neurofibromas	Nf1^-/- skin-derived glial precursors	Nf1^+/- background/Unclear^a
Pheochromocytomas	Nf1^-/- chromaffin cells	Unclear
Early CNS gliomas	Nf1^-/- astrocytes	None^b
Early glial tumors	Nf1^-/- glia	None
Myeloid leukemia	Nf1^-/- myeloid cells	None
Other symptoms
Café-au-lait macules	Nf1^-/- melanocytes	Unclear
Pseudoarthroses	Nf1^-/- or Nf1^+/- connective tissue	Unclear
Osteoporosis	Nf1^+/- osteoblasts Nf1^+/- osteoclasts	Unknown^c
Cognitive deficits	Nf1^+/- neurons	Unknown
Vascular disease	Nf1^+/- endothelia Nf1^+/- vascular smooth muscle	Unknown

“Unclear” indicates that the data were derived from mice and/or human samples with a heterozygous Nf1/NF1 background but that a firm conclusion has not been made as to whether the condition requires this background.

“None” indicates that these symptoms can emerge despite wild-type supporting cells.

“Unknown” indicates that while Nf1 haploinsufficiency appears to be sufficient for pathogenesis, the possibility of undetected cooperating events cannot be ruled out. These data principally derive from studies in both mice and humans.