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Combinatorial Developmental Controls on Striatonigral Circuits.

ABSTRACT: Cortical pyramidal cells are generated locally, from pre-programmed progenitors, to form functionally distinct areas. By contrast, striatal projection neurons (SPNs) are generated remotely from a common source, undergo migration to form mosaics of striosomes and matrix, and become incorporated into functionally distinct sectors. Striatal circuits might thus have a unique logic of developmental organization, distinct from those of the neocortex. We explore this possibility in mice by mapping one set of SPNs, those in striosomes, with striatonigral projections to the dopamine-containing substantia nigra pars compacta (SNpc). Same-age SPNs exhibit topographic striatonigral projections, according to their resident sector. However, the different birth dates of resident SPNs within a given sector specify the destination of their axons within the SNpc. These findings highlight a logic intercalating birth date-dependent and birth date-independent factors in determining the trajectories of SPN axons and organizing specialized units of striatonigral circuitry that could influence behavioral expression and vulnerabilities to disease.

SUBMITTER: Matsushima A

PROVIDER: S-EPMC7433760 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Combinatorial Developmental Controls on Striatonigral Circuits.

Matsushima Ayano A Graybiel Ann M AM

Cell reports 20200601 11

Cortical pyramidal cells are generated locally, from pre-programmed progenitors, to form functionally distinct areas. By contrast, striatal projection neurons (SPNs) are generated remotely from a common source, undergo migration to form mosaics of striosomes and matrix, and become incorporated into functionally distinct sectors. Striatal circuits might thus have a unique logic of developmental organization, distinct from those of the neocortex. We explore this possibility in mice by mapping one ...[more]

PMID: 32553154

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Project description:Striatal projection neurons comprise two populations of striatonigral and striatopallidal neurons. These two neuronal populations play distinct roles in controlling movement-related functions in the basal ganglia circuits. An important issue is how striatal progenitors are developmentally specified into these two distinct neuronal populations. In the present study, we characterized the function of Islet-1 (Isl1), a LIM-homeodomain transcription factor, in striatal development. Genetic fate mapping showed that Isl1(+) progeny specifically developed into a subpopulation of striatonigral neurons that transiently expressed Isl1. In Nestin-Cre;Isl1(f/f) KO mouse brain, differentiation of striatonigral neurons was defective, as evidenced by decreased expression of striatonigral-enriched genes, including substance P, prodynorphin, solute carrier family 35, member D3 (Slc35d3), and PlexinD1. Striatonigral axonal projections were also impaired, and abnormal apoptosis was observed in Isl1 KO striatum. It was of particular interest that striatopallidal-enriched genes, including dopamine D2 receptor (Drd2), proenkephalin, A2A adenosine receptor (A2aR) and G protein-coupled receptor 6 (Gpr6), were concomitantly up-regulated in Isl1 mutant striatum, suggesting derepression of striatopallidal genes in striatonigral neurons in the absence of Isl1. The suppression of striatopallidal genes by Isl1 was further examined by overexpression of Isl1 in the striatum of Drd2-EGFP transgenic mice using in utero electroporation. Ectopic Isl1 expression was sufficient to repress Drd2-EGFP signals in striatopallidal neurons. Taken together, our study suggests that Isl1 specifies the cell fate of striatonigral neurons not only by orchestrating survival, differentiation, and axonal projections of striatonigral neurons but also by suppressing striatopallidal-enriched genes. The dual action of developmental control by Isl1 in promoting appropriate striatonigral but repressing inappropriate striatopallidal genetic profiles may ensure sharpening of the striatonigral identity during development.

Dataset Information

Combinatorial Developmental Controls on Striatonigral Circuits.

Publications

Combinatorial Developmental Controls on Striatonigral Circuits.

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