Serotonergic regulation of bipolar cell survival in the developing cerebral cortex

Wong, Fong Kuan; Selten, Martijn; Rosés-Novella, Claudia; Pallas‐Bazarra, Noemí; Serafeimidou‐Pouliou, Eleni; Hanusz-Godoy, Alicia; Oozeer, Fazal; Edwards, Robert H.; Marı́n, Oscar

doi:10.1016/j.celrep.2022.111037

Cited by 11 publications

(16 citation statements)

References 84 publications

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“…Given the key role Pcdhγc4 plays in the survival of cINs and the fact that Pcdhγc4 is a cell-adhesion molecule that is involved in homophilic cell-cell recognition (Thu et al, 2014), initial cell-cell interactions within the cIN population could be mediated through Pcdhγc4. Other studies have shown that programmed cell death is also regulated at least in part through activity-dependent mechanisms (Duan et al, 2020;Wong et al, 2018Wong et al, , 2022. It remains undetermined what role, if any, Pcdhγc4 plays in the regulation of activity during the peak of programmed cell death.…”

Section: Exogenous Expression Of Pcdhγc4 In Pcdhγ Knockout Cins Rescu...mentioning

confidence: 99%

The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex

Leon¹,

Steffen²,

Dale-Huang³

et al. 2023

Preprint

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Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers are adjusted by programmed cell death. Previously, we showed that loss of clustered gamma protocadherins (Pcdhγ), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice. Here we show that the sole deletion of the Pcdhγc4 isoform, but not of the other 21 isoforms in the Pcdhγ gene cluster, increased cIN cell death in mice during the normal period of programmed cell death. Viral expression of the Pcdhγc4 isoform rescued transplanted cINs lacking Pcdhγ from cell death. We conclude that Pcdhγ, specifically Pcdhγc4, plays a critical role in regulating the survival of cINs during their normal period of cell death. This demonstrates a novel specificity in the role of Pcdhγ isoforms in cortical development.

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Section: Exogenous Expression Of Pcdhγc4 In Pcdhγ Knockout Cins Rescu...mentioning

confidence: 99%

The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex

Leon¹,

Steffen²,

Dale-Huang³

et al. 2023

Preprint

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“…There are several mechanisms that could regulate survival, spatial distribution and maturation of MGE-derived interneuron subtypes following transplantation. First, activity-dependent mechanisms -such as excitatory pyramidal cell activity -may serve as a critical regulator of interneuron development establishing age-and region-specific permissive corridors for MGE progenitors [43][44][45] . In murine neocortex, for example, spontaneous patterns of activity present at birth [46][47][48] could facilitate the widespread anterior-to-posterior migration of transplanted MGE progenitors seen here (Fig.…”

Section: Discussionmentioning

confidence: 99%

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Paterno,

Vu,

Hsieh

et al. 2024

Preprint

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Interneuron progenitor transplantation can ameliorate disease symptoms in a variety of neurological disorders. This strategy is based on transplantation of embryonic medial ganglionic eminence (MGE) progenitors. Elucidating host brain environment influences on interneuron progenitors as they integrate is critical to optimizing this strategy across different disease states. Here, we systematically evaluated age and brain region influences on survival, migration and differentiation of transplant-derived cells. We find that early postnatal MGE transplantation yields superior survival and more extensive migratory capabilities compared to juvenile or adult. MGE progenitors migrate more widely in cortex compared to hippocampus. Maturation to interneuron subtypes is regulated by age and brain region. MGE progenitors transplanted into dentate gyrus sub-region of early postnatal hippocampus can differentiate into astrocytes. Our results suggest that host brain environment critically regulates survival, spatial distribution and maturation of MGE-derived interneurons following transplantation. These findings inform and enable optimal conditions for interneuron transplant therapies.

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“…Increased activity also correlates with improved postnatal survival of cortical interneurons ( Denaxa et al, 2018 ; Priya et al, 2018 ; Wong et al, 2018 , 2022 ). Interneurons that die are less likely to participate in coordinated network events, displaying fewer synchronized calcium fluctuations in vivo compared with cells that survive ( Duan et al, 2020 ; Wong et al, 2018 ).…”

Section: Calcium-dependent Regulation Of Cellular Behaviors In the De...mentioning

confidence: 95%

“…Interestingly, the contribution of activity-dependent signaling to interneuron survival, thought to be mediated at least partly through the calcium-sensitive CaN/NFAT pathway ( Priya et al, 2018 ), is subtype-specific ( Denaxa et al, 2018 ; Priya et al, 2018 ). The activity of maturing neuronal populations also non-cell autonomously regulates interneuron subtype survival to shape developing circuits ( Wong et al, 2018 , 2022 ). Glutamatergic signaling is required for activity-dependent survival of neurogliaform and basket cells, whereas bipolar cells rely on serotonin to modulate activity-dependent survival ( Wong et al, 2022 ).…”

Section: Calcium-dependent Regulation Of Cellular Behaviors In the De...mentioning

confidence: 99%

“…The activity of maturing neuronal populations also non-cell autonomously regulates interneuron subtype survival to shape developing circuits ( Wong et al, 2018 , 2022 ). Glutamatergic signaling is required for activity-dependent survival of neurogliaform and basket cells, whereas bipolar cells rely on serotonin to modulate activity-dependent survival ( Wong et al, 2022 ). It will be interesting to determine the calcium-dependent pathways that link electrical signals to the survival of specific neuronal subtypes.…”

Section: Calcium-dependent Regulation Of Cellular Behaviors In the De...mentioning

confidence: 99%

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Calcium and activity-dependent signaling in the developing cerebral cortex

2022

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Calcium influx can be stimulated by various intra- and extracellular signals to set coordinated gene expression programs into motion. As such, the precise regulation of intracellular calcium represents a nexus between environmental cues and intrinsic genetic programs. Mounting genetic evidence points to a role for the deregulation of intracellular calcium signaling in neuropsychiatric disorders of developmental origin. These findings have prompted renewed enthusiasm for understanding the roles of calcium during normal and dysfunctional prenatal development. In this Review, we describe the fundamental mechanisms through which calcium is spatiotemporally regulated and directs early neurodevelopmental events. We also discuss unanswered questions about intracellular calcium regulation during the emergence of neurodevelopmental disease, and provide evidence that disruption of cell-specific calcium homeostasis and/or redeployment of developmental calcium signaling mechanisms may contribute to adult neurological disorders. We propose that understanding the normal developmental events that build the nervous system will rely on gaining insights into cell type-specific calcium signaling mechanisms. Such an understanding will enable therapeutic strategies targeting calcium-dependent mechanisms to mitigate disease.

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Serotonergic regulation of bipolar cell survival in the developing cerebral cortex

Cited by 11 publications

References 84 publications

The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex

The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Calcium and activity-dependent signaling in the developing cerebral cortex

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