| 2004 |
Sp9 (and Sp8) are expressed in the apical ectodermal ridge (AER) and act as positive regulators of Fgf8 expression during limb outgrowth; they are ectodermal targets of Fgf10 signaling from the mesenchyme. Dominant-negative overexpression in chick and morpholino knockdown in zebrafish both abolish Fgf8 expression and impair limb outgrowth, demonstrating their requirement. Wnt/beta-catenin signaling positively regulates Sp8 but not Sp9. |
Embryological and genetic analyses, chick overexpression and dominant-negative approaches, zebrafish morpholino knockdown, in situ hybridization |
Development (Cambridge, England) |
High |
15358670
|
| 2016 |
Sp9 is expressed in LGE progenitors and maintained in postmitotic striatopallidal MSNs. Sp9-null mice lose most striatopallidal (D2-type) MSNs due to decreased proliferation of their progenitors and increased Bax-dependent apoptosis, while striatonigral neurons are largely unaffected. ChIP-qPCR shows Ascl1 directly binds the Sp9 promoter. RNA-seq/ISH reveal Sp9 promotes expression of Adora2a, P2ry1, Gpr6, and Grik3 in the LGE and striatum. |
Sp9-null mouse genetic analysis, ChIP-qPCR, RNA-seq, in situ hybridization, immunofluorescence |
Cell reports |
High |
27452460
|
| 2018 |
SP8 and SP9 coordinately drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone, which is required for D2 MSN production. ChIP-Seq demonstrates SP9 directly binds the promoter and a putative enhancer of Six3. Conditional deletion of Sp8 and Sp9 causes loss of virtually all D2 MSNs due to reduced neurogenesis; Six3 conditional deletion phenocopies this. |
Conditional knockout mouse genetics (Sp8/Sp9 double mutants), ChIP-Seq (SP9), RNA-seq, in situ hybridization, genetic epistasis (Six3 conditional KO) |
Development (Cambridge, England) |
High |
29967281
|
| 2018 |
Sp8 and Sp9 are co-expressed in neuroblasts and interneurons of the V-SVZ-RMS-OB system. Although Sp9-null mice show no major OB interneuron defect alone, conditional deletion of both Sp8 and Sp9 severely reduces OB interneuron number through defects in neuronal differentiation, tangential and radial migration, and increased cell death. Sp8/Sp9 double mutants fail to express Prokr2 and Tshz1 in newly born neuroblasts. |
Conditional knockout mouse genetics (Sp8/Sp9 single and double mutants), RNA-Seq, RNA in situ hybridization, cell counting, migration analysis |
Cerebral cortex (New York, N.Y. : 1991) |
High |
28981617
|
| 2019 |
SP9 is expressed in the MGE subventricular zone and in MGE-derived migrating interneurons. Sp9-null and conditional mutant mice show ~50% reduction in MGE-derived cortical interneurons, ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased SST+/PV+ ratio. ChIP-Seq and RNA-Seq identify SP9 as a direct transcriptional regulator of Arx, Lhx6, Lhx8, Nkx2-1, Zeb2 (interneuron development factors) and Ackr3, Epha3, St18 (migration genes). |
Sp9-null and conditional knockout mouse genetics, SP9 ChIP-Seq, RNA-Seq, immunofluorescence, in situ hybridization |
Cerebral cortex (New York, N.Y. : 1991) |
High |
29878134
|
| 2019 |
SP8 and SP9 are co-expressed in the SVZ of the dorsal CGE. Conditional knockout of Sp8/9 (Gsx2-Cre or Dlx5/6-CIE lines) causes severe loss of CGE-derived cortical interneurons and migration defects (longer leading processes, ectopic accumulation in the CGE). Sp8/9 coordinately repress expression of Pak3, Robo1, and Slit1 to regulate CGE-derived interneuron migration. |
Conditional knockout mouse genetics (Gsx2-Cre and Dlx5/6-CIE lines), immunofluorescence, in situ hybridization, RNA-Seq |
The Journal of comparative neurology |
High |
31070778
|
| 2019 |
SP8 protein is upregulated in MGE mantle zone in Sp9-null mutants. Combined Sp8/Sp9 conditional knockout results in severe loss of PV+ cortical interneurons due to tangential migration defects, more severe than Sp9 single mutants, indicating Sp8 and Sp9 cooperate. Sp8/Sp9 activity regulates MGE-derived cortical interneuron migration at least through controlling EphA3, Ppp2r2c, and Rasgef1b expression. |
Sp9-null and Sp8/Sp9 conditional knockout mouse genetics, immunofluorescence, RNA-Seq, migration analysis |
Frontiers in molecular neuroscience |
Medium |
31001083
|
| 2022 |
Sp9-positive LGE progenitors produce both D1-MSNs and D2-MSNs, but Sp9 expression is rapidly downregulated in postmitotic D1-MSNs. Sustained Sp9 expression (gain-of-function) in LGE progenitors and descendants promotes D2-MSN identity and represses D1-MSN identity, causing an imbalance between D1- and D2-MSNs. Fate-changed D2-like MSNs survive normally in adulthood. |
Genetic fate mapping, gain-of-function (sustained Sp9 expression) mouse model, immunofluorescence, in situ hybridization |
Cell death discovery |
Medium |
35773249
|
| 2024 |
De novo heterozygous SP9 variants cause interneuronopathy. SP9 missense variants affecting glutamate 378 (within the conserved DNA-binding domain) result in severe epileptic encephalopathy via hypomorphic and neomorphic DNA-binding effects, demonstrated by in vitro assays. SP9 loss-of-function variants result in milder neurodevelopmental phenotype. This establishes that altered SP9 DNA-binding activity directly causes disease. |
In silico and in vitro assays of SP9 variant DNA-binding activity, patient cohort variant analysis, international data-sharing |
Genetics in medicine : official journal of the American College of Medical Genetics |
Medium |
38288683
|
| 2025 |
Sp9 was identified as a key regulator of visual thalamic fate through in silico predictions and in vivo perturbations in a spatiotemporal single-cell multiomic atlas of the embryonic mouse thalamus, indicating Sp9 governs sensory lineage specification within the thalamus. |
Single-cell multiomic atlas, spatial transcriptomics, barcoding-based lineage tracing, in vivo perturbations |
bioRxiv (preprint)preprint |
Low |
bio_10.1101_2025.07.17.665342
|