Figure 4.

A MB-Specific Enhancer Directs Expression in Catecholaminergic Populations of Neurons Known to Parkinson Disease Biology

(A) An IGV track indicating the location of the MB-specific region of open chromatin located in intron 4 of Snca.

(B) Snca is differentially expressed between the MB and FB DA neurons. The red bar is the mean expression of the four replicates (black dots).

(C) At 72 hpf, stable transgenic zebrafish reporter assays indicate this putative CRE is capable of directing reporter expression in key catecholaminergic neuronal populations, including the locus coeruleus (LC), the catecholaminergic tract (CT) of the hindbrain, the diencephalic cluster (DC), and the subpallium (SP), into which the DC projects.

(D–H) Further studies in lacZ reporter assays in embryonic (E) and post-natal (P) mice indicate dynamic enhancer usage across developmental time.

(D) This enhancer directs expression throughout the MB, FB, dorsal root ganglia (DRG), sympathetic chain (SC), and cranial nerves (CN) of E12.5 mice.

(E) By E15.5, reporter expression is observed in the amygdala and/or piriform cortex (AM/PC), sympathetic chain, MB, and hypothalamus (Hyp).

(F) Patterns of reporter expression at P7 reflect those seen at E15.5.

(G) Reporter activity is observed at P30 in the amygdala; hypothalamus and thalamus (Thal); brain stem (BS); substantia nigra (SN); ventral tegmental area (VTA); and the periaqueductal gray area (PAG).

(H) In aged mice (P574), reporter expression is detected robustly in the brain stem and faintly in the amygdala.