An Early Cortical Progenitor-Specific Mechanism Regulates Thalamocortical Innervation

Pal, Suranjana; Dwivedi, Deepanjali; Pramanik, Tuli; Godbole, Geeta; Iwasato, Takuji; Jabaudon, Denis; Bhalla, Upinder S.; Tole, Shubha

doi:10.1523/jneurosci.0226-21.2021

Cited by 12 publications

(14 citation statements)

References 62 publications

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“…GSEA revealed that the biological processes associated with synaptic transmission, sensory perception, and protein localization to cilium were enriched in Lhx2 flox/ flox ovaries. In the brain, Lhx2 is involved in the development and patterning of the neurons involved in sensory perception [51,52]. In hypothalamic tanycytes, Lhx2 regulates the numbers of motile cilia by controlling the expression of FoxJ1 [53].…”

Section: Discussionmentioning

confidence: 99%

Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary

Singh

Bhide

et al. 2022

Experimental Cell Research

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Section: Discussionmentioning

confidence: 99%

Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary

Singh

Bhide

et al. 2022

Experimental Cell Research

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“…These findings also offer novel insights into how LHX2 adapts its roles at different stages of neurogenesis. Previous studies identified an early cortical progenitor-specific role of LHX2 that regulates the electrophysiological properties of the firstborn cells of the cortex, the subplate (27).…”

Section: Discussionmentioning

confidence: 99%

“…In utero electroporation was performed at E15.5 as previously described ( 27 ). Embryos were injected with plasmid DNA solution dissolved in nuclease-free water with 0.1% fast green with plasmid DNA into the lateral ventricle through the uterine wall using a fine glass microcapillary (Sutter capillaries #B100-75-10).…”

Section: Methodsmentioning

confidence: 99%

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LHX2 regulates dendritic morphogenesis in layer II/III of the neocortex via distinct pathways in progenitors and postmitotic neurons

Bose,

Ravindran,

Kumari

et al. 2024

Preprint

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In the mammalian neocortex, excitatory neurons that send projections via the corpus callosum are critical to integrating information across the two brain hemispheres. The molecular mechanisms governing the development of the dendritic arbours and spines of these callosal neurons are poorly understood, yet these features are critical to their physiological properties. LIM Homeodomain 2 (Lhx2), a regulator of fundamental processes in cortical development, is expressed in postmitotic callosal neurons occupying layer II/III of the neocortex and also in their progenitors in the embryonic day (E) 15.5 ventricular zone of the mouse neocortex. We tested whether this factor is essential for dendritic arbour configuration and spine morphogenesis of layer II/III neurons. Here, we report loss of Lhx2 either in postmitotic callosal neurons or their progenitors, resulting in shrunken dendritic arbours and perturbed spine morphology. In postmitotic neurons, we identified that LHX2 regulates dendritic and spine morphogenesis via the canonical Wnt/β Catenin signalling pathway. Constitutive activation of this pathway in postmitotic neurons recapitulates the Lhx2 loss-of-function phenotype. In E15.5 progenitors, we identified that bHLH transcription factor Neurog2 mediates LHX2 function in regulating dendritic and spine morphogenesis. We show that Neurog2 expression increases upon loss of Lhx2 and that shRNA-mediated Neurog2 knockdown rescues the loss of Lhx2 phenotype. Our study uncovers novel LHX2 functions in cortical circuit assembly consistent with its temporally dynamic and multifunctional roles in development.

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“…Primers for genotyping were (expected band sizes): In utero, electroporation was performed as previously described (71). Embryos were injected with 1-2 μL of plasmid DNA solution dissolved in nuclease-free water with 0.1% fast green with plasmid DNA into the lateral ventricle through the uterine wall using a fine glass microcapillary (Sutter capillaries #B100-75-10).…”

Section: Micementioning

confidence: 99%

Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signaling pathway

Bose,

Talwar,

Suresh

et al. 2023

Preprint

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In the developing vertebrate central nervous system, neurons and glia typically arise sequentially from common progenitors. Here, we report that the transcription factor Forkhead Box G1 (Foxg1) regulates gliogenesis in the mouse neocortex via distinct cell-autonomous roles in progenitors and in postmitotic neurons that regulate different aspects of the gliogenic FGF signalling pathway. We demonstrate that loss ofFoxg1in cortical progenitors at neurogenic stages causes premature astrogliogenesis. We identify a novel FOXG1 target, the pro-gliogenic FGF pathway componentFgfr3, which is suppressed by FOXG1 cell-autonomously to maintain neurogenesis. Furthermore, FOXG1 can also suppress premature astrogliogenesis triggered by the augmentation of FGF signalling. We identify a second novel function of FOXG1 in regulating the expression of gliogenic ligand FGF18 in new born neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons increasesFgf18expression and enhances gliogenesis in the progenitors. These results fit well with the model that new born neurons secrete cues that trigger progenitors to produce the next wave of cell types, astrocytes. If FGF signalling is attenuated inFoxg1null progenitors, they progress to oligodendrocyte production. Therefore, loss of FOXG1 transitions the progenitor to a gliogenic state, producing either astrocytes or oligodendrocytes depending on FGF signalling levels. Our results uncover how FOXG1 integrates extrinsic signalling via the FGF pathway to regulate the sequential generation of neurons, astrocytes, and oligodendrocytes in the cerebral cortex.Significance StatementFunctional brain circuitry requires the correct numbers and subtypes of neurons and glia. A fundamental feature of the vertebrate central nervous system is that common progenitors produce first neurons and then glia. Cell-intrinsic factors modulate how a progenitor responds to cell-extrinsic cues to achieve this transition. Here, we report that the transcription factor Forkhead Box G1 (Foxg1) regulates gliogenesis in the mouse neocortexin vivoby regulating different aspects of the gliogenic FGF signalling pathway in progenitors and in postmitotic neurons. Loss ofFoxg1results in premature gliogenesis via regulation of novel targetsFgfr3in progenitors andFgf18in postmitotic neurons. Our findings offer mechanistic insight into FOXG1 syndrome, an Autism Spectrum Disorder caused byFoxg1mutations in humans.

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An Early Cortical Progenitor-Specific Mechanism Regulates Thalamocortical Innervation

Cited by 12 publications

References 62 publications

Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary

Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary

LHX2 regulates dendritic morphogenesis in layer II/III of the neocortex via distinct pathways in progenitors and postmitotic neurons

Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signaling pathway

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