The crux of Cux genes in neuronal function and plasticity

Weiss, Linnea A.; Nieto, Marta

doi:10.1016/j.brainres.2018.02.044

Cited by 24 publications

(21 citation statements)

References 129 publications

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“…CUX2 expression in multiple neuronal classes at different phases of differentiation suggests its diverse roles in development. Indeed, prior studies in animal models found CUX2 primarily as a layer-specific regulator playing a role in dendritic branching, spine formation and synapse regulation [25,28,56]. Our results show that CUX2 is present in different neuronal populations that are either migrating or are forming first cortical synapses and circuits in transient zones SP and MZ.…”

Section: Diverse Roles Of Cux2supporting

confidence: 49%

Adult Upper Cortical Layer Specific Transcription Factor CUX2 Is Expressed in Transient Subplate and Marginal Zone Neurons of the Developing Human Brain

Miškić

Kostović

Rašin

et al. 2021

Cells

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Cut-Like Homeobox 2 (Cux2) is a transcription factor involved in dendrite and spine development, and synapse formation of projection neurons placed in mouse upper neocortical layers. Therefore, Cux2 is often used as an upper layer marker in the mouse brain. However, expression of its orthologue CUX2 remains unexplored in the human fetal neocortex. Here, we show that CUX2 protein is expressed in transient compartments of developing neocortical anlage during the main fetal phases of neocortical laminar development in human brain. During the early fetal phase when neurons of the upper cortical layers are still radially migrating to reach their final place in the cortical anlage, CUX2 was expressed in the marginal zone (MZ), deep cortical plate, and pre-subplate. During midgestation, CUX2 was still expressed in the migrating upper cortical neurons as well as in the subplate (SP) and MZ neurons. At the term age, CUX2 was expressed in the gyral white matter along with its expected expression in the upper layer neurons. In sum, CUX2 was expressed in migratory neurons of prospective superficial layers and in the diverse subpopulation of transient postmigratory SP and MZ neurons. Therefore, our findings indicate that CUX2 is a novel marker of distinct transient, but critical histogenetic events during corticogenesis. Given the Cux2 functions reported in animal models, our data further suggest that the expression of CUX2 in postmigratory SP and MZ neurons is associated with their unique dendritic and synaptogenesis characteristics.

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Section: Diverse Roles Of Cux2supporting

confidence: 49%

Adult Upper Cortical Layer Specific Transcription Factor CUX2 Is Expressed in Transient Subplate and Marginal Zone Neurons of the Developing Human Brain

Miškić

Kostović

Rašin

et al. 2021

Cells

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“…The intratelencephalic (IT) PyNs constitute the largest top-level class and mediate the vast majority of intracortical, inter-hemispheric, and cortico-striatal communication streams 1, 43–45 . The Cux1 and Cux2 are Cut-repeat containing homeodomain TFs predominantly expressed in supragranular IT PyNs and their progenitors 46–48 . Cux expression is thought to begin at the transition from progenitor to postmitotic neurons 47, 49 , thus may initiate and then maintain the identity of IT PyNs.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, a number of TFs used in this study continue to evolve across mammalian species from rodents to primates and human 75 and might contribute to the development of human-specific traits. For example, Cux1 is located in the human accelerated region (HAR) of the human genome 76 , and the regulation of Cux1 , Fezf2 , Tbr1 , Tbr2 , and Foxp2 continues to evolve and diverge in primates and is implicated in several developmental disorders such as autism 35, 48, 65 . Therefore, these TF mouse driver lines may provide crucial handles to track the developmental trajectories of PyN subpopulations in the convoluted process of cortical circuit assembly, with implications in the evolutionary history of PyNs in human cortex.…”

Section: Discussionmentioning

confidence: 99%

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Genetic dissection of glutamatergic neuron subpopulations and developmental trajectories in the cerebral cortex

Matho

Huilgol

Galbavy

et al. 2020

Preprint

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Diverse types of glutamatergic pyramidal neurons (PyNs) mediate the myriad processing streams and output channels of the cerebral cortex, yet all derive from neural progenitors of the embryonic dorsal telencephalon. Here, we establish genetic strategies and tools for dissecting and fate mapping PyN subpopulations based on their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target the temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen of temporally inducible mouse Cre and Flp knock-in driver lines to enable combinatorial targeting of major progenitor types and projection classes. Intersectional converter lines confer viral access to specific subsets defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for multi-modal characterization of PyN subpopulations and tracking their developmental trajectories toward elucidating the organization and assembly of cortical processing networks and output channels.

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“…IT PyNs constitute the largest top-level class and mediate intracortical and corticostriatal communication streams 1 , 19 – 21 . Cux1 and Cux2 are predominantly expressed in supragranular IT PyNs and their progenitors 22 , 23 . In our Cux1-CreER;Ai14 mice, postnatal tamoxifen induction prominently labelled L2–L4 PyNs dorsal to the rhinal fissure as well as a set of hippocampal PyNs, recapitulating the endogenous pattern (Fig.…”

Section: Targeting Pyn Subpopulationsmentioning

confidence: 99%

Genetic dissection of the glutamatergic neuron system in cerebral cortex

Matho

Huilgol

Galbavy

et al. 2021

Nature

146

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Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels.

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The crux of Cux genes in neuronal function and plasticity

Cited by 24 publications

References 129 publications

Adult Upper Cortical Layer Specific Transcription Factor CUX2 Is Expressed in Transient Subplate and Marginal Zone Neurons of the Developing Human Brain

Adult Upper Cortical Layer Specific Transcription Factor CUX2 Is Expressed in Transient Subplate and Marginal Zone Neurons of the Developing Human Brain

Genetic dissection of glutamatergic neuron subpopulations and developmental trajectories in the cerebral cortex

Genetic dissection of the glutamatergic neuron system in cerebral cortex

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