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Brain Research Feb 2019A hundred years after Lhx2 ortholog apterous was identified as a critical regulator of wing development in Drosophila, LIM-HD gene family members have proved to be... (Review)
Review
A hundred years after Lhx2 ortholog apterous was identified as a critical regulator of wing development in Drosophila, LIM-HD gene family members have proved to be versatile and powerful components of the molecular machinery that executes the blueprint of embryogenesis across vertebrate and invertebrate species. Here, we focus on the spatio-temporally varied functions of LIM-homeodomain transcription factor LHX2 in the developing mouse forebrain. Right from its earliest known role in telencephalic and eye field patterning, to the control of the neuron-glia cell fate switch, and the regulation of axon pathfinding and dendritic arborization in late embryonic stages, LHX2 has been identified as a fundamental, temporally dynamic, always necessary, and often sufficient factor in a range of critical developmental phenomena. While Lhx2 mutant phenotypes have been characterized in detail in multiple brain structures, only recently have we advanced in our understanding of the molecular mechanisms by which this factor acts. Common themes emerge from how this multifunctional molecule controls a range of developmental steps in distinct forebrain structures. Examining these shared features, and noting unique aspects of LHX2 function is likely to inform our understanding of how a single factor can bring about a diversity of effects and play central and critical roles across systems and stages. The parallels in LHX2 and APTEROUS functions, and the protein complexes they participate in, offer insights into evolutionary strategies that conserve tool kits and deploy them to play new, yet familiar roles in species separated by hundreds of millions of years.
Topics: Animals; Biological Evolution; Cell Differentiation; Gene Expression Regulation, Developmental; Homeodomain Proteins; LIM-Homeodomain Proteins; Mice; Neurogenesis; Neuroglia; Neurons; Prosencephalon; Spatio-Temporal Analysis; Transcription Factors
PubMed: 29522720
DOI: 10.1016/j.brainres.2018.02.046 -
Philosophical Transactions of the Royal... Jan 2020Vocalization is an ancient vertebrate trait essential to many forms of communication, ranging from courtship calls to free verse. Vocalizations may be entirely innate... (Review)
Review
Vocalization is an ancient vertebrate trait essential to many forms of communication, ranging from courtship calls to free verse. Vocalizations may be entirely innate and evoked by sexual cues or emotional state, as with many types of calls made in primates, rodents and birds; volitional, as with innate calls that, following extensive training, can be evoked by arbitrary sensory cues in non-human primates and corvid songbirds; or learned, acoustically flexible and complex, as with human speech and the courtship songs of oscine songbirds. This review compares and contrasts the neural mechanisms underlying innate, volitional and learned vocalizations, with an emphasis on functional studies in primates, rodents and songbirds. This comparison reveals both highly conserved and convergent mechanisms of vocal production in these different groups, despite their often vast phylogenetic separation. This similarity of central mechanisms for different forms of vocal production presents experimentalists with useful avenues for gaining detailed mechanistic insight into how vocalizations are employed for social and sexual signalling, and how they can be modified through experience to yield new vocal repertoires customized to the individual's social group. This article is part of the theme issue 'What can animal communication teach us about human language?'
Topics: Animals; Birds; Brain Mapping; Emotions; Female; Humans; Language; Learning; Male; Mammals; Motor Cortex; Neurobiology; Neurons; Phylogeny; Primates; Prosencephalon; Songbirds; Vocalization, Animal; Volition
PubMed: 31735150
DOI: 10.1098/rstb.2019.0054 -
Developmental Dynamics : An Official... Aug 2019Evolutionary conservation and experimental tractability have made animal model systems invaluable tools in our quest to understand human embryogenesis, both normal and... (Review)
Review
Evolutionary conservation and experimental tractability have made animal model systems invaluable tools in our quest to understand human embryogenesis, both normal and abnormal. Standard genetic approaches, particularly useful in understanding monogenic diseases, are no longer sufficient as research attention shifts toward multifactorial outcomes. Here, we examine this progression through the lens of holoprosencephaly (HPE), a common human malformation involving incomplete forebrain division, and a classic example of an etiologically complex outcome. We relate the basic underpinning of HPE pathogenesis to critical cell-cell interactions and signaling molecules discovered through embryological and genetic approaches in multiple model organisms, and discuss the role of the mouse model in functional examination of HPE-linked genes. We then outline the most critical remaining gaps to understanding human HPE, including the conundrum of incomplete penetrance/expressivity and the role of gene-environment interactions. To tackle these challenges, we outline a strategy that leverages new and emerging technologies in multiple model systems to solve the puzzle of HPE.
Topics: Animals; Gene-Environment Interaction; Holoprosencephaly; Humans; Mice; Models, Animal; Penetrance; Prosencephalon; Signal Transduction
PubMed: 30993762
DOI: 10.1002/dvdy.41 -
The Journal of Comparative Neurology Mar 2024The brain is spatially organized into subdivisions, nuclei and areas, which often correspond to functional and developmental units. A segmentation of brain regions in...
The brain is spatially organized into subdivisions, nuclei and areas, which often correspond to functional and developmental units. A segmentation of brain regions in the form of a consensus atlas facilitates mechanistic studies and is a prerequisite for sharing information among neuroanatomists. Gene expression patterns objectively delineate boundaries between brain regions and provide information about their developmental and evolutionary histories. To generate a detailed molecular map of the larval zebrafish diencephalon, we took advantage of the Max Planck Zebrafish Brain (mapzebrain) atlas, which aligns hundreds of transcript and transgene expression patterns in a shared coordinate system. Inspection and co-visualization of close to 50 marker genes have allowed us to resolve the tripartite prosomeric scaffold of the diencephalon at unprecedented resolution. This approach clarified the genoarchitectonic partitioning of the alar diencephalon into pretectum (alar part of prosomere P1), thalamus (alar part of prosomere P2, with habenula and pineal complex), and prethalamus (alar part of prosomere P3). We further identified the region of the nucleus of the medial longitudinal fasciculus, as well as the posterior and anterior parts of the posterior tuberculum, as molecularly distinct basal parts of prosomeres 1, 2, and 3, respectively. Some of the markers examined allowed us to locate glutamatergic, GABAergic, dopaminergic, serotoninergic, and various neuropeptidergic domains in the larval zebrafish diencephalon. Our molecular neuroanatomical approach has thus (1) yielded an objective and internally consistent interpretation of the prosomere boundaries within the zebrafish forebrain; has (2) produced a list of markers, which in sparse combinations label the subdivisions of the diencephalon; and is (3) setting the stage for further functional and developmental studies in this vertebrate brain.
Topics: Animals; Zebrafish; Larva; Diencephalon; Thalamus; Prosencephalon
PubMed: 37983970
DOI: 10.1002/cne.25549 -
Development, Growth & Differentiation May 2017In the current model, the most anterior part of the forebrain (secondary prosencephalon) is subdivided into the telencephalon dorsally and the hypothalamus ventrally.... (Review)
Review
In the current model, the most anterior part of the forebrain (secondary prosencephalon) is subdivided into the telencephalon dorsally and the hypothalamus ventrally. Our recent study identified a new morphogenetic unit named the optic recess region (ORR) between the telencephalon and the hypothalamus. This modification of the forebrain regionalization based on the ventricular organization resolved some previously unexplained inconsistency about regional identification in different vertebrate groups. The ventricular-based comparison also revealed a large diversity within the subregions (notably in the hypothalamus and telencephalon) among different vertebrate groups. In tetrapods there is only one hypothalamic recess, while in teleosts there are two recesses. Most notably, the mammalian and teleost hypothalami are two extreme cases: the former has lost the cerebrospinal fluid-contacting (CSF-c) neurons, while the latter has increased them. Thus, one to one homology of hypothalamic subregions in mammals and teleosts requires careful verification. In the telencephalon, different developmental processes between Sarcopterygii (lobe-finned fish) and Actinopterygii (ray-finned fish) have already been described: the evagination and the eversion. Although pallial homology has been long discussed based on the assumption that the medial-lateral organization of the pallium in Actinopterygii is inverted from that in Sarcopterygii, recent developmental data contradict this assumption. Current models of the brain organization are largely based on a mammalian-centric point of view, but our comparative analyses shed new light on the brain organization of Osteichthyes.
Topics: Animals; Fishes; Neurogenesis; Prosencephalon; Telencephalon
PubMed: 28470718
DOI: 10.1111/dgd.12348 -
Autonomic Neuroscience : Basic &... Mar 2015This brief review discusses the current state of knowledge regarding the cortical circuitry associated with autonomic cardiovascular responses to volitional exercise in... (Review)
Review
This brief review discusses the current state of knowledge regarding the cortical circuitry associated with autonomic cardiovascular responses to volitional exercise in conscious humans. Studies to date have emphasized the autonomic nervous system adjustments that occur through top-down central command features as well as bottom-up signals arising from skeletal muscle. While in its infancy, the pattern of cortical circuitry associated with exercise seem to depend on the nature of the exercise but with common patterns arising in the insula cortex, dorsal anterior cingulate cortex, medial prefrontal cortex, and hippocampus.
Topics: Animals; Autonomic Nervous System; Cardiovascular System; Humans; Prosencephalon
PubMed: 25458433
DOI: 10.1016/j.autneu.2014.10.022 -
Neuron Jan 2022Thermoregulatory behavior is a basic motivated behavior for body temperature homeostasis. Despite its fundamental importance, a forebrain region or defined neural...
Thermoregulatory behavior is a basic motivated behavior for body temperature homeostasis. Despite its fundamental importance, a forebrain region or defined neural population required for this process has yet to be established. Here, we show that Vgat-expressing neurons in the lateral hypothalamus (LH neurons) are required for diverse thermoregulatory behaviors. The population activity of LH neurons is increased during thermoregulatory behavior and bidirectionally encodes thermal punishment and reward (P&R). Although this population also regulates feeding and caloric reward, inhibition of parabrachial inputs selectively impaired thermoregulatory behaviors and encoding of thermal stimulus by LH neurons. Furthermore, two-photon calcium imaging revealed a subpopulation of LH neurons bidirectionally encoding thermal P&R, which is engaged during thermoregulatory behavior, but is largely distinct from caloric reward-encoding LH neurons. Our data establish LH neurons as a required neural substrate for behavioral thermoregulation and point to the key role of the thermal P&R-encoding LH subpopulation in thermoregulatory behavior.
Topics: Body Temperature Regulation; Hypothalamic Area, Lateral; Neurons; Prosencephalon; Reward
PubMed: 34687664
DOI: 10.1016/j.neuron.2021.09.039 -
Nature Apr 2024The human nervous system is a highly complex but organized organ. The foundation of its complexity and organization is laid down during regional patterning of the neural...
The human nervous system is a highly complex but organized organ. The foundation of its complexity and organization is laid down during regional patterning of the neural tube, the embryonic precursor to the human nervous system. Historically, studies of neural tube patterning have relied on animal models to uncover underlying principles. Recently, models of neurodevelopment based on human pluripotent stem cells, including neural organoids and bioengineered neural tube development models, have emerged. However, such models fail to recapitulate neural patterning along both rostral-caudal and dorsal-ventral axes in a three-dimensional tubular geometry, a hallmark of neural tube development. Here we report a human pluripotent stem cell-based, microfluidic neural tube-like structure, the development of which recapitulates several crucial aspects of neural patterning in brain and spinal cord regions and along rostral-caudal and dorsal-ventral axes. This structure was utilized for studying neuronal lineage development, which revealed pre-patterning of axial identities of neural crest progenitors and functional roles of neuromesodermal progenitors and the caudal gene CDX2 in spinal cord and trunk neural crest development. We further developed dorsal-ventral patterned microfluidic forebrain-like structures with spatially segregated dorsal and ventral regions and layered apicobasal cellular organizations that mimic development of the human forebrain pallium and subpallium, respectively. Together, these microfluidics-based neurodevelopment models provide three-dimensional lumenal tissue architectures with in vivo-like spatiotemporal cell differentiation and organization, which will facilitate the study of human neurodevelopment and disease.
Topics: Humans; Body Patterning; Cell Culture Techniques, Three Dimensional; Cell Differentiation; Microfluidics; Neural Crest; Neural Tube; Pluripotent Stem Cells; Prosencephalon; Spinal Cord
PubMed: 38408487
DOI: 10.1038/s41586-024-07204-7 -
Current Opinion in Neurobiology Feb 2017Tight control of developmental timing is pivotal to many major processes in developmental biology, such as patterning, fate specification, cell cycle dynamics, cell... (Review)
Review
Tight control of developmental timing is pivotal to many major processes in developmental biology, such as patterning, fate specification, cell cycle dynamics, cell migration and connectivity. Temporal change in these ontogenetic sequences is known as heterochrony, a major force in the evolution of body plans and organogenesis. In the last 5 years, studies in fish and rodents indicate that heterochrony in signaling during early development generates diversity in forebrain size and complexity. Here, we summarize these findings and propose that, additionally to spatio-temporal tuning of neurogenesis, temporal and quantitative modulation of signaling events drive pivotal changes in shape, size and complexity of the forebrain across evolution, participating to the generation of diversity in animal behavior and emergence of cognition.
Topics: Animals; Biological Evolution; Cell Movement; Neurogenesis; Prosencephalon; Time Factors
PubMed: 28092740
DOI: 10.1016/j.conb.2016.12.008 -
Nature Reviews. Molecular Cell Biology May 2021
Topics: Cell Shape; Humans; Prosencephalon
PubMed: 33782586
DOI: 10.1038/s41580-021-00364-8