Abstract
Striatal medium-sized spiny neurons (MSNs), composed of striatonigral and striatopallidal neurons, are derived from the lateral ganglionic eminence (LGE). We find that the transcription factor Sp9 is expressed in LGE progenitors that generate nearly all striatal MSNs and that Sp9 expression is maintained in postmitotic striatopallidal MSNs. Sp9-null mice lose most striatopallidal MSNs because of decreased proliferation of striatopallidal MSN progenitors and increased Bax-dependent apoptosis, whereas the development of striatonigral neurons is largely unaffected. ChIP qPCR provides evidence that Ascl1 directly binds the Sp9 promoter. RNA-seq and insitu hybridization reveal that Sp9 promotes expression of Adora2a, P2ry1, Gpr6, and Grik3 in the LGE and striatum. Thus, Sp9 is crucial for the generation, differentiation, and survival of striatopallidal MSNs.
Highlights
The striatum is the largest component of the basal ganglia
Sp9 Is Widely Expressed in the lateral ganglionic eminence (LGE), medial ganglionic eminence (MGE), and Caudal Ganglionic Eminence To systematically study the expression and function of the transcriptional factors (TFs) Sp9 in the telencephalon, we generated Sp9 polyclonal antibodies and several Sp9 mutant alleles
Immunocytochemistry of Sp9 and Sp9-LacZ (b-galactosidase [b-gal]) and in situ Sp9 RNA hybridization demonstrated that Sp9 RNA and Sp9 protein were widely expressed in the subventricular zone (SVZ) and mantle zone of the LGE, MGE, and CGE at E13.5 (Figures 1E–1H)
Summary
The striatum (caudate nucleus and putamen) is the largest component of the basal ganglia. Two major subtypes of MSNs send outputs to other components of the basal ganglia: striatonigral (direct pathway) and striatopallidal (indirect pathway). Striatonigral MSNs express the dopamine D1 receptor (Drd1) and neuropeptide Tac (known as substance P), whereas striatopallidal MSNs express the dopamine D2 receptor (Drd2) and neuropeptide enkephalin (Enk) (Gerfen, 1992; Gerfen et al, 1990; Gerfen and Surmeier, 2011; Kawaguchi et al, 1990). About 5%–10% of neurons in the striatum are aspiny interneurons. They are choline acetyltransferase (ChAT)+, parvalbumin (PV)+, somatostatin (SST)+ and calretinin (CR)+ (Kawaguchi et al, 1995)
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