miR-193b-365 microcluster downstream of coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons.

Different neuron types develop characteristic axonal and dendritic arborizations that determine their inputs, outputs, and functions. Expression of fate-determinant transcription factors is essential for specification of their distinct identities. However, the mechanisms downstream of fate-determinant factors coordinating different aspects of neuron identity are not understood.

Loss of Zmiz1 in mice leads to impaired cortical development and autistic-like behaviors.

De novo mutations in transcriptional regulators are emerging as key risk factors contributing to the etiology of neurodevelopmental disorders. Human genetic studies have recently identified ZMIZ1 and its de novo mutations as causal of a neurodevelopmental syndrome strongly associated with intellectual disability, autism, ADHD, microcephaly, and other developmental anomalies. However, the role of ZMIZ in brain development or how ZMIZ1 mutations cause neurological phenotypes is unknown.

Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics.

Background: Traumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity and heterogeneity of the affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within tissues. This study focuses on the hippocampal sub-regions, analyzing proteomic expression profiles in mice at the acute (1 day) and subacute (7 days) phases of post-TBI to understand subregion-specific vulnerabilities and long-term consequences.

Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown.

Zmiz1 is a novel regulator of brain development associated with autism and intellectual disability.

Neurodevelopmental disorders (NDDs) are a class of pathologies arising from perturbations in brain circuit formation and maturation with complex etiological triggers often classified as environmental and genetic. Neuropsychiatric conditions such as autism spectrum disorders (ASD), intellectual disability (ID), and attention deficit hyperactivity disorders (ADHD) are common NDDs characterized by their hereditary underpinnings and inherent heterogeneity. Genetic risk factors for NDDs are increasingly being identified in non-coding regions and proteins bound to them, including transcriptional regulators and chromatin remodelers.

Symmetry in levels of axon-axon homophilic adhesion establishes topography in the corpus callosum and development of connectivity between brain hemispheres.

Specific and highly diverse connectivity between functionally specialized regions of the nervous system is controlled at multiple scales, from anatomically organized connectivity following macroscopic axon tracts to individual axon target-finding and synapse formation. Identifying mechanisms that enable entire subpopulations of related neurons to project their axons with regional specificity within stereotyped tracts to form appropriate long-range connectivity is key to understanding brain development, organization, and function. Here, we investigate how axons of the cerebral cortex form precise connections between the two cortical hemispheres via the corpus callosum.

Hippocampal memory reactivation during sleep is correlated with specific cortical states of the retrosplenial and prefrontal cortices.

Episodic memories are thought to be stabilized through the coordination of cortico-hippocampal activity during sleep. However, the timing and mechanism of this coordination remain unknown. To investigate this, we studied the relationship between hippocampal reactivation and slow-wave sleep up and down states of the retrosplenial cortex (RTC) and prefrontal cortex (PFC).

Tle4 controls both developmental acquisition and early post-natal maturation of corticothalamic projection neuron identity.

Identities of distinct neuron subtypes are specified during embryonic development, then maintained during post-natal maturation. In cerebral cortex, mechanisms controlling early acquisition of neuron-subtype identities have become increasingly understood. However, mechanisms controlling neuron-subtype identity stability during post-natal maturation are largely unexplored.

Zmiz1 is a novel regulator of lymphatic endothelial cell gene expression and function.

Zinc Finger MIZ-Type Containing 1 (Zmiz1), also known as ZIMP10 or RAI17, is a transcription cofactor and member of the Protein Inhibitor of Activated STAT (PIAS) family of proteins. Zmiz1 is critical for a variety of biological processes including vascular development. However, its role in the lymphatic vasculature is unknown.

Characterization and manipulation of Corticothalamic neurons in associative cortices using Syt6-Cre transgenic mice.

Corticothalamic interactions between associative cortices and higher order thalamic nuclei are involved in high-cognitive functions such as decision-making and working memory. Corticothalamic neurons (CTn) in the prefrontal cortex and other associative areas have been much less studied than their counterparts in the primary sensory areas. The availability of characterized transgenic tools to study CTn in associative areas will facilitate their study and contribute to overcome the scarcity of data about their properties, network dynamics, and contribution to cognitive functions.

Deregulated Rac1 Activity in Neural Crest Controls Cell Proliferation, Migration and Differentiation During Midbrain Development.

Mutations in allele are implicated in multiple brain tumors, indicating a rigorous control of Rac1 activity is required for neural tissue normal development and homeostasis. To understand how elevated Rac1 activity affects neural crest cells (NCCs) development, we have generated mice, in which a constitutively active Rac1 mutant is expressed specifically in NCCs derivatives. Our results revealed that augmented Rac1 activity leads to enlarged midbrain and altered cell density, accompanied by increased NCCs proliferation rate and misrouted cell migration.

Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity.

Corticothalamic projection neurons (CThPN) are a diverse set of neurons, critical for function of the neocortex. CThPN development and diversity need to be precisely regulated, but little is known about molecular controls over their differentiation and functional specialization, critically limiting understanding of cortical development and complexity. We report the identification of a set of genes that both define CThPN and likely control their differentiation, diversity, and function.

Cux1 Enables Interhemispheric Connections of Layer II/III Neurons by Regulating Kv1-Dependent Firing.

Neuronal subtype-specific transcription factors (TFs) instruct key features of neuronal function and connectivity. Activity-dependent mechanisms also contribute to wiring and circuit assembly, but whether and how they relate to TF-directed neuronal differentiation is poorly investigated. Here we demonstrate that the TF Cux1 controls the formation of the layer II/III corpus callosum (CC) projections through the developmental transcriptional regulation of Kv1 voltage-dependent potassium channels and the resulting postnatal switch to a Kv1-dependent firing mode.

RORβ induces barrel-like neuronal clusters in the developing neocortex.

Neurons in layer IV of the rodent whisker somatosensory cortex are tangentially organized in periodic clusters called barrels, each of which is innervated by thalamocortical axons transmitting sensory information from a single principal whisker, together forming a somatotopic map of the whisker pad. Proper thalamocortical innervation is critical for barrel formation during development, but the molecular mechanisms controlling layer IV neuron clustering are unknown. Here, we investigate the role in this mapping of the nuclear orphan receptor RORβ, which is expressed in neurons in layer IV during corticogenesis.

Thalamic input to distal apical dendrites in neocortical layer 1 is massive and highly convergent.

Input to apical dendritic tufts is now deemed crucial for associative learning, attention, and similar "feedback" interactions in the cerebral cortex. Excitatory input to apical tufts in neocortical layer 1 has been traditionally assumed to be predominantly cortical, as thalamic pathways directed to this layer were regarded relatively scant and diffuse. However, the sensitive tracing methods used in the present study show that, throughout the rat neocortex, large numbers (mean approximately 4500/mm(2)) of thalamocortical neurons converge in layer 1 and that this convergence gives rise to a very high local density of thalamic terminals.

[Diversity in thalamic relay neurons: evidence for "bottom-up" and "top-down" information flow in thalamocortical pathways].

Thalamocortical (TC) pathways are still mainly understood as the gateway for ascending sensory-motor information into the cortex. However, it is now clear that a great many TC cells are involved in interactions between cortical areas via the thalamus. We review recent data, including our own, which demonstrate the generalized presence in rodent thalamus of two major TC cell types characterized, among other features, by their axon development, arborization and laminar targeting in the cortex.

Embryonic and postnatal development of the layer I-directed ("matrix") thalamocortical system in the rat.

Inputs to the layer I apical dendritic tufts of pyramidal cells are crucial in "top-down" interactions in the cerebral cortex. A large population of thalamocortical cells, the "matrix" (M-type) cells, provides a direct robust input to layer I that is anatomically and functionally different from the thalamocortical input to layer VI. The developmental timecourse of M-type axons is examined here in rats aged E (embryonic day) 16 to P (postnatal day) 30.

Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain.

Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons.

Reelin-immunoreactive neurons, axons, and neuropil in the adult ferret brain: evidence for axonal secretion of reelin in long axonal pathways.

Reelin is a large secretable protein which, when developmentally defective, causes the reeler brain malformation in mice and a recessive form of lissencephaly with cerebellar hypoplasia in humans. In addition, Reelin is heavily expressed throughout the adult brain, although its function/s there are still poorly understood. To gain insight into which adult neuronal circuits may be under the influence of Reelin, we systematically mapped Reelin-immunoreactive neuronal somata, axons, and neuropil in the brain and brainstem of ferrets.

Reelin immunoreactivity in the adult primate brain: intracellular localization in projecting and local circuit neurons of the cerebral cortex, hippocampus and subcortical regions.

Reelin is a large secretable protein which is widely expressed by specific neuronal populations. In the embryonic brain, Reelin plays a signaling role critical for the correct positioning of migrating neuroblasts. Reelin is also expressed in the adult mammalian brain, including humans; however, its function/s there remain poorly understood.