TY - JOUR
T1 - Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins
AU - Pereira Luppi, Milagros
AU - Azcorra, Maite
AU - Caronia-Brown, Giuliana
AU - Poulin, Jean Francois
AU - Gaertner, Zachary
AU - Gatica, Serafin
AU - Moreno-Ramos, Oscar Andrés
AU - Nouri, Navid
AU - Dubois, Marilyn
AU - Ma, Yongchao C.
AU - Ramakrishnan, Charu
AU - Fenno, Lief
AU - Kim, Yoon Seok
AU - Deisseroth, Karl
AU - Cicchetti, Francesca
AU - Dombeck, Daniel A.
AU - Awatramani, Rajeshwar
N1 - Funding Information:
We thank Michael Wegner (guinea pig anti-Sox6 antibody), Maria Grazia Spillantini (human anatomical boundaries), Vasileios Papakis (confocal imaging), and Matthew Schipma (RNA-seq analysis). This work was supported by NIH grants R01-NS119690 , R01-NS096240 , R01-MH110555 , R21-NS092034-01A1 , P50 DA044121-01A1 , and 1 F31 NS122481-01A1 .
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/11/9
Y1 - 2021/11/9
N2 - Dopamine (DA) neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson's disease, while those in the dorsal tier are relatively spared. Defining the molecular, functional, and developmental characteristics of each SNc tier is crucial to understand their distinct susceptibility. We demonstrate that Sox6 expression distinguishes ventrally and dorsally biased DA neuron populations in the SNc. The Sox6+ population in the ventral SNc includes an Aldh1a1+ subset and is enriched in gene pathways that underpin vulnerability. Sox6+ neurons project to the dorsal striatum and show activity correlated with acceleration. Sox6− neurons project to the medial, ventral, and caudal striatum and respond to rewards. Moreover, we show that this adult division is encoded early in development. Overall, our work demonstrates a dual origin of the SNc that results in DA neuron cohorts with distinct molecular profiles, projections, and functions.
AB - Dopamine (DA) neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson's disease, while those in the dorsal tier are relatively spared. Defining the molecular, functional, and developmental characteristics of each SNc tier is crucial to understand their distinct susceptibility. We demonstrate that Sox6 expression distinguishes ventrally and dorsally biased DA neuron populations in the SNc. The Sox6+ population in the ventral SNc includes an Aldh1a1+ subset and is enriched in gene pathways that underpin vulnerability. Sox6+ neurons project to the dorsal striatum and show activity correlated with acceleration. Sox6− neurons project to the medial, ventral, and caudal striatum and respond to rewards. Moreover, we show that this adult division is encoded early in development. Overall, our work demonstrates a dual origin of the SNc that results in DA neuron cohorts with distinct molecular profiles, projections, and functions.
KW - Aldh1a1
KW - Calb1
KW - Parkinson's
KW - Sox6
KW - dopamine
KW - dorsal SNc
KW - fate map
KW - selective vulnerability
KW - ventral SNc
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U2 - 10.1016/j.celrep.2021.109975
DO - 10.1016/j.celrep.2021.109975
M3 - Article
C2 - 34758317
AN - SCOPUS:85118856032
VL - 37
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 6
M1 - 109975
ER -