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Experimental Gerontology Aug 2017In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the... (Review)
Review
In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions.
Topics: Age Factors; Aging; Animals; Cell Movement; Cell Proliferation; Humans; Lateral Ventricles; Neural Stem Cells; Neurogenesis; Olfactory Bulb; Prosencephalon; Species Specificity; Stem Cell Niche
PubMed: 27867091
DOI: 10.1016/j.exger.2016.11.007 -
Development (Cambridge, England) Jun 2024The vertebrate Dlx gene family encode homeobox transcription factors that are related to the Drosophila Distal-less (Dll) gene and are crucial for development. Over the... (Review)
Review
The vertebrate Dlx gene family encode homeobox transcription factors that are related to the Drosophila Distal-less (Dll) gene and are crucial for development. Over the last ∼35 years detailed information has accrued about the redundant and unique expression and function of the six mammalian Dlx family genes. DLX proteins interact with general transcriptional regulators, and co-bind with other transcription factors to enhancer elements with highly specific activity in the developing forebrain. Integration of the genetic and biochemical data has yielded a foundation for a gene regulatory network governing the differentiation of forebrain GABAergic neurons. In this Primer, we describe the discovery of vertebrate Dlx genes and their crucial roles in embryonic development. We largely focus on the role of Dlx family genes in mammalian forebrain development revealed through studies in mice. Finally, we highlight questions that remain unanswered regarding vertebrate Dlx genes despite over 30 years of research.
Topics: Animals; Prosencephalon; Homeodomain Proteins; Transcription Factors; Gene Expression Regulation, Developmental; Humans; Mammals; Mice
PubMed: 38819455
DOI: 10.1242/dev.202684 -
Methods in Molecular Biology (Clifton,... 2022Hedgehog signaling pathway shapes our body by regulating proliferation and differentiation of cells. The spatial and temporal distribution pattern of its ligands finely...
Hedgehog signaling pathway shapes our body by regulating proliferation and differentiation of cells. The spatial and temporal distribution pattern of its ligands finely controls the activity of the Hedgehog pathway during development. To mimic the active regulation of Hedgehog pathway, we have developed a light-inducible Hedgehog signaling activator 6-nitroveratryloxy-carbonyl Smoothened agonist (NVOC-SAG). Here we describe a method to selectively induce ventral differentiation of human iPS cell-derived forebrain organoids in a light-dependent manner. This article describes preparation of NVOC-SAG, culture of iPS cell-derived forebrain organoids, light irradiation, and downstream analyses.
Topics: Cell Differentiation; Hedgehog Proteins; Humans; Organoids; Prosencephalon; Signal Transduction
PubMed: 34562253
DOI: 10.1007/978-1-0716-1701-4_16 -
The International Journal of... 2020The forebrain roof plate undergoes dramatic morphogenetic changes to invaginate, and this leads to formation of the two cerebral hemispheres. While many genetic factors... (Review)
Review
The forebrain roof plate undergoes dramatic morphogenetic changes to invaginate, and this leads to formation of the two cerebral hemispheres. While many genetic factors are known to regulate this process, the mechanism of forebrain roof plate invagination remains unknown. In a recent study we have identified retinoic acid as a signal from the dorsal mesenchyme that regulates the invagination of the roof plate. This has brought into focus the importance of the interaction between the dorsal mesenchyme and the underlying roof plate. One of the structures derived from the dorso-medial forebrain after roof plate invagination is the hippocampus. While the functions of the hippocampus are conserved between birds and mammals, there are distinct structural differences. We have studied hippocampus development in the chick embryo and uncovered several similarities and differences between the process in mammals and birds. This study has also lent support to one of the prevalent models of structural homology between the avian and mammalian hippocampus. In this review, we have underscored the importance of the chick embryo as a model for studying forebrain roof plate morphogenesis and hippocampus development.
Topics: Animals; Chick Embryo; Embryonic Induction; Hippocampus; Morphogenesis; Prosencephalon
PubMed: 32659013
DOI: 10.1387/ijdb.190143js -
Cellular and Molecular Life Sciences :... Jul 2016The components of the nervous system are assembled in development by the process of cell migration. Although the principles of cell migration are conserved throughout... (Review)
Review
The components of the nervous system are assembled in development by the process of cell migration. Although the principles of cell migration are conserved throughout the brain, different subsystems may predominantly utilize specific migratory mechanisms, or may display unusual features during migration. Examining these subsystems offers not only the potential for insights into the development of the system, but may also help in understanding disorders arising from aberrant cell migration. The olfactory system is an ancient sensory circuit that is essential for the survival and reproduction of a species. The organization of this circuit displays many evolutionarily conserved features in vertebrates, including molecular mechanisms and complex migratory pathways. In this review, we describe the elaborate migrations that populate each component of the olfactory system in rodents and compare them with those described in the well-studied neocortex. Understanding how the components of the olfactory system are assembled will not only shed light on the etiology of olfactory and sexual disorders, but will also offer insights into how conserved migratory mechanisms may have shaped the evolution of the brain.
Topics: Animals; Biological Evolution; Cell Movement; Hypothalamus; Neurons; Olfactory Bulb; Olfactory Cortex; Olfactory Pathways; Prosencephalon; Rodentia; Smell; Vomeronasal Organ
PubMed: 26994098
DOI: 10.1007/s00018-016-2172-7 -
Neuroscience and Biobehavioral Reviews Feb 2018Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.-... (Review)
Review
Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance.
Topics: Animals; Glucose; Homeostasis; Humans; Neurons; Prefrontal Cortex; Prosencephalon; Taste
PubMed: 28455231
DOI: 10.1016/j.neubiorev.2017.04.024 -
Neuron Jan 2015The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making... (Review)
Review
The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making it imperative to understand the underlying genetic circuitry. Recent progress now makes it possible to begin fully elucidating the genomic regulatory mechanisms that control forebrain gene expression. Herein, we discuss the current knowledge of how transcription factors drive gene expression programs through their interactions with cis-acting genomic elements, such as enhancers; how analyses of chromatin and DNA modifications provide insights into gene expression states; and how these approaches yield insights into the evolution of the human brain.
Topics: Animals; Enhancer Elements, Genetic; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Genomics; Humans; Prosencephalon; Transcription Factors; Transcription, Genetic
PubMed: 25569346
DOI: 10.1016/j.neuron.2014.11.011 -
Biochemistry. Biokhimiia Mar 2017Neuronal plastic rearrangements during the development and functioning of neurons are largely regulated by trophic factors, including nerve growth factor (NGF). NGF is... (Review)
Review
Neuronal plastic rearrangements during the development and functioning of neurons are largely regulated by trophic factors, including nerve growth factor (NGF). NGF is also involved in the pathogenesis of Alzheimer's disease. In the brain, NGF is produced in structures innervated by basal forebrain cholinergic neurons and retrogradely transported along the axons to the bodies of cholinergic neurons. NGF is essential for normal development and functioning of the basal forebrain; it affects formation of the dendritic tree and modulates the activities of choline acetyltransferase and acetylcholinesterase in basal forebrain neurons. The trophic effect of NGF is mediated through its interactions with TrkA and p75 receptors. Experimental and clinical studies have shown that brain levels of NGF are altered in various pathologies. However, the therapeutic use of NGF is limited by its poor ability to penetrate the blood-brain barrier, adverse side effects that are due to the pleiotropic action of this factor, and the possibility of immune response to NGF. For this reason, the development of gene therapy methods for treating NGF deficit-associated pathologies is of particular interest. Another approach is creation of low molecular weight NGF mimetics that would interact with the corresponding receptors and display high biological activity but be free of the unfavorable effects of NGF.
Topics: Animals; Blood-Brain Barrier; Cholinergic Neurons; Humans; Nerve Growth Factor; Neuronal Plasticity; Prosencephalon
PubMed: 28320270
DOI: 10.1134/S0006297917030075 -
BioEssays : News and Reviews in... Aug 2014Fezf1 and Fezf2 are highly conserved transcription factors that were first identified by their specific expression in the anterior neuroepithelium of Xenopus and... (Review)
Review
Fezf1 and Fezf2 are highly conserved transcription factors that were first identified by their specific expression in the anterior neuroepithelium of Xenopus and zebrafish embryos. These proteins share an N-terminal domain with homology to the canonical engrailed repressor motif and a C-terminal DNA binding domain containing six C2H2 zinc-finger repeats. Over a decade of study indicates that the Fez proteins play critical roles during nervous system development in species as diverse as fruit flies and mice. Herein we discuss recent progress in understanding the functions of Fezf1 and Fezf2 in neurogenesis and cell fate specification during mammalian nervous system development. Going forward we believe that efforts should focus on understanding how expression of these factors is precisely regulated, and on identifying target DNA sequences and interacting partners. Such knowledge may reveal the mechanisms by which Fezf1 and Fezf2 accomplish both independent and redundant functions across diverse tissue and cell types.
Topics: Animals; Body Patterning; Evolution, Molecular; Gene Expression Regulation, Developmental; Humans; Neural Stem Cells; Neurogenesis; Olfactory Cortex; Prosencephalon; Repressor Proteins; Transcription Factors
PubMed: 24913420
DOI: 10.1002/bies.201400039 -
Cellular and Molecular Life Sciences :... Aug 2014Embryonic stem cells (ESCs) have been used extensively as in vitro models of neural development and disease, with special efforts towards their conversion into forebrain... (Review)
Review
Embryonic stem cells (ESCs) have been used extensively as in vitro models of neural development and disease, with special efforts towards their conversion into forebrain progenitors and neurons. The forebrain is the most complex brain region, giving rise to several fundamental structures, such as the cerebral cortex, the hypothalamus, and the retina. Due to the multiplicity of signaling pathways playing different roles at distinct times of embryonic development, the specification and patterning of forebrain has been difficult to study in vivo. Research performed on ESCs in vitro has provided a large body of evidence to complement work in model organisms, but these studies have often been focused more on cell type production than on cell fate regulation. In this review, we systematically reassess the current literature in the field of forebrain development in mouse and human ESCs with a focus on the molecular mechanisms of early cell fate decisions, taking into consideration the specific culture conditions, exogenous and endogenous molecular cues as described in the original studies. The resulting model of early forebrain induction and patterning provides a useful framework for further studies aimed at reconstructing forebrain development in vitro for basic research or therapy.
Topics: Animals; Embryonic Stem Cells; Humans; Neurogenesis; Prosencephalon; Signal Transduction
PubMed: 24643740
DOI: 10.1007/s00018-014-1596-1