Dopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons

Turcato, Flavia; Wegman, Elliot; Lü, Tao; Ferguson, Nathan; Luo, Yu

doi:10.1016/j.isci.2022.105278

Cited by 9 publications

(2 citation statements)

References 45 publications

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“…Mice were perfused with 4% PFA and drop-fixed overnight before being transferred to 20% sucrose, followed by 30% sucrose once the tissue had sunk. Then tissue was sectioned on a cryostat in 30 μm thickness and subjected to IHC as previously described 106 . Antibodies for GFP (1:1000, Invitrogen or 1:500, Aves), IBA1 (1:500, Abcam or 1:1000, Wako), P2RY12 (1:500, Biolegend), TMEM119 (1:2000, GeneTex), GFAP (1:1000, Sigma), NEUN (1:1000, Biolegend), CD68 (1:4000, BioRad), MBP (1:250, BioRad), CC1 (1:250, Millipore Sigma), Olig2 (1:500, RND Systems), NG2 (1:250, Millipore), Parvalbumin (1:1000, Swant), Somatostatin (1:250, Santa Cruz), Ki67 (1:300, Invitrogen) and pSMAD3 (1:150, Abcam) were used.…”

Section: Methodsmentioning

confidence: 99%

Adult microglial TGFβ1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice

Bedolla,

Wegman,

Weed

et al. 2024

Nat Commun

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While TGF-β signaling is essential for microglial function, the cellular source of TGF-β1 ligand and its spatial regulation remains unclear in the adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to the activation of microglia featuring a dyshomeostatic transcriptome that resembles disease-associated, injury-associated, and aged microglia, suggesting microglial self-produced TGF-β1 ligands are important in the adult CNS. Astrocytes in MG-Tgfb1 inducible (i)KO mice show a transcriptome profile that is closely aligned with an LPS-associated astrocyte profile. Additionally, using sparse mosaic single-cell microglia KO of TGF-β1 ligand we established an autocrine mechanism for signaling. Here we show that MG-Tgfb1 iKO mice present cognitive deficits, supporting that precise spatial regulation of TGF-β1 ligand derived from microglia is required for the maintenance of brain homeostasis and normal cognitive function in the adult brain.

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Section: Methodsmentioning

confidence: 99%

Adult microglial TGFβ1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice

Bedolla,

Wegman,

Weed

et al. 2024

Nat Commun

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“…In addition to a survival cell autonomous effect on dopaminergic neurons themselves, the authors showed that Shh triggers a response in the striatum, received by dopaminergic projections, which secretes Glial-cell-line-Derived Neurotrophic Factor as a survival factor for dopaminergic neurons. More recently, these results were debated, as another study did not reproduce the findings [190]. Using genetic fate mapping (using the Shh-CreERT mouse line), the authors show that perinatal or young adult TH-positive neurons are not generated from the Shh lineage.…”

Section: Axonal Transport and Neuronal Communicationmentioning

confidence: 99%

Establishing Hedgehog Gradients during Neural Development

Douceau

Guerrero

Ferent

2023

Cells

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A morphogen is a signaling molecule that induces specific cellular responses depending on its local concentration. The concept of morphogenic gradients has been a central paradigm of developmental biology for decades. Sonic Hedgehog (Shh) is one of the most important morphogens that displays pleiotropic functions during embryonic development, ranging from neuronal patterning to axon guidance. It is commonly accepted that Shh is distributed in a gradient in several tissues from different origins during development; however, how these gradients are formed and maintained at the cellular and molecular levels is still the center of a great deal of research. In this review, we first explored all of the different sources of Shh during the development of the nervous system. Then, we detailed how these sources can distribute Shh in the surrounding tissues via a variety of mechanisms. Finally, we addressed how disrupting Shh distribution and gradients can induce severe neurodevelopmental disorders and cancers. Although the concept of gradient has been central in the field of neurodevelopment since the fifties, we also describe how contemporary leading-edge techniques, such as organoids, can revisit this classical model.

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