Mef2c Controls Postnatal Callosal Axon Targeting by Regulating Sensitivity to Ephrin Repulsion DOI Creative Commons
Sriram Sudarsanam,

Luis Guzman-Clavel,

Nyle Dar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Cortical connectivity is contingent on ordered emergence of neuron subtypes followed by the formation subtype-specific axon projections. Intracortical circuits, including long-range callosal projections, are crucial for information processing, but mechanisms intracortical targeting still unclear. We find that transcription factor Myocyte enhancer 2-c (Mef2c) directs development somatosensory cortical (S1) layer 4 and 5 pyramidal neurons during embryogenesis. During early postnatal development, Mef2c expression shifts to 2/3 projection (L2/3 CPNs), we a novel function in homotopic contralateral regions S1-L2/3 CPNs. demonstrate, using functional manipulation EphA-EphrinA signaling Mef2c- mutant CPNs, downregulates EphA 6 desensitize CPN axons EphrinA5-repulsion at their targets. Our work uncovers dual roles development: regulation laminar subtype specification embryogenesis, neurons. required L4 L5 embryonic neocortex Postnatally, enriched L2/3 L2/3-specific deletion leads EphA6 upregulation sensitizes them EfnA5 repulsion cortex.

Язык: Английский

Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices DOI Creative Commons
Yanqi Liu, Pol Bech, Keita Tamura

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Май 17, 2024

Long-range axonal projections of diverse classes neocortical excitatory neurons likely contribute to brain-wide interactions processing sensory, cognitive and motor signals. Here, we performed light-sheet imaging fluorescently labeled axons from genetically defined located in posterior primary somatosensory barrel cortex supplemental cortex. We used convolutional networks segment axon-containing voxels quantified their distribution within the Allen Mouse Brain Atlas Common Coordinate Framework. Axonal density was analyzed for different glutamatergic using transgenic mouse lines selectively expressing Cre recombinase layer 2/3 intratelencephalic projection (Rasgrf2-dCre), 4 (Scnn1a-Cre), 5 (Tlx3-Cre), pyramidal tract (Sim1-Cre), (Rbp4-Cre), 6 corticothalamic (Ntsr1-Cre). found distinct neuronal many downstream brain areas, which were largely similar supplementary cortices. Functional connectivity maps obtained optogenetic activation sensory wide-field revealed topographically organized evoked activity frontal with more laterally signaling anteriorly regions cortex, consistent anatomical projections. The current methodology therefore appears quantify innervation patterns supporting signaling.

Язык: Английский

Процитировано

3

Computational Generation of Long-range Axonal Morphologies DOI Creative Commons
Adrien Berchet, Rémy Petkantchin, Henry Markram

и другие.

Neuroinformatics, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 10, 2025

Abstract Long-range axons are fundamental to brain connectivity and functional organization, enabling communication between different regions. Recent advances in experimental techniques have yielded a substantial number of whole-brain axonal reconstructions. While previous computational generative models neurons predominantly focused on dendrites, generating realistic morphologies is more challenging due their distinct targeting. In this study, we present novel algorithm for axon synthesis that combines algebraic topology with the Steiner tree algorithm, an extension minimum spanning tree, generate both local long-range compartments axons. We demonstrate our computationally generated closely replicate data terms morphological properties. This approach enables generation biologically accurate span large distances connect multiple regions, advancing digital reconstruction brain. Ultimately, opens up new possibilities large-scale in-silico simulations, research into function disorders.

Язык: Английский

Процитировано

0

Mef2c Controls Postnatal Callosal Axon Targeting by Regulating Sensitivity to Ephrin Repulsion DOI Creative Commons
Sriram Sudarsanam,

Luis Guzman-Clavel,

Nyle Dar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Cortical connectivity is contingent on ordered emergence of neuron subtypes followed by the formation subtype-specific axon projections. Intracortical circuits, including long-range callosal projections, are crucial for information processing, but mechanisms intracortical targeting still unclear. We find that transcription factor Myocyte enhancer 2-c (Mef2c) directs development somatosensory cortical (S1) layer 4 and 5 pyramidal neurons during embryogenesis. During early postnatal development, Mef2c expression shifts to 2/3 projection (L2/3 CPNs), we a novel function in homotopic contralateral regions S1-L2/3 CPNs. demonstrate, using functional manipulation EphA-EphrinA signaling Mef2c- mutant CPNs, downregulates EphA 6 desensitize CPN axons EphrinA5-repulsion at their targets. Our work uncovers dual roles development: regulation laminar subtype specification embryogenesis, neurons. required L4 L5 embryonic neocortex Postnatally, enriched L2/3 L2/3-specific deletion leads EphA6 upregulation sensitizes them EfnA5 repulsion cortex.

Язык: Английский

Процитировано

0