biostudies-literatureTurcato FCOffice of the DirectorNIA NIH HHSNIEHS NIH HHSNINDS NIH HHSNational Institutes of HealthNIH HHSNINDS105278https://www.ebi.ac.uk/biostudies/studies/S-EPMC9587326biostudies-literatureUnknown25(11)A model was previously proposed that DA neurons provide SHH ligand to striatal interneurons, which in turn support the survival of DA neurons through the release of trophic factors such as Glial cell-derived neurotrophic factor (GDNF). However, some key clinical observations do not support this proposed model, and a recent independent study shows that striatal cholinergic neuron survival does not rely on intact DA neuron projections. To resolve this discrepancy, we generated several independent mouse lines to examine the exact role of DA neuron-derived <i>Shh</i> signaling in the maintenance of the basal ganglia circuit and to identify the <i>Shh</i>-producing cells in the adult brain. Our data suggest that the deletion of <i>Shh</i> in DA neurons does not affect DA neuron survival or locoiScienceDopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons.PMC9587326R01 AG083164R01 NS091213R01 NS125074R01NS091213S10 OD030402S10OD030402R01 NS107365T32 ES007250R01NS107365R01 NS094152Ferguson NTurcato FCLu TWegman ELuo YfalseDopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons.A model was previously proposed that DA neurons provide SHH ligand to striatal interneurons, which in turn support the survival of DA neurons through the release of trophic factors such as Glial cell-derived neurotrophic factor (GDNF). However, some key clinical observations do not support this proposed model, and a recent independent study shows that striatal cholinergic neuron survival does not rely on intact DA neuron projections. To resolve this discrepancy, we generated several independent mouse lines to examine the exact role of DA neuron-derived <i>Shh</i> signaling in the maintenance of the basal ganglia circuit and to identify the <i>Shh</i>-producing cells in the adult brain. Our data suggest that the deletion of <i>Shh</i> in DA neurons does not affect DA neuron survival or loco2022-01-01T00:00:00Z2022 Nov2026-05-28T01:19:35.583Z2025-02-18T23:29:38.782ZS-EPMC95873263628145410.1016/j.isci.2022.105278