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Seminars in Cell & Developmental Biology Nov 2020Embryonic boundaries were first described in Drosophila, and then in vertebrate embryos, as cellular interfaces between compartments. They display signaling properties... (Review)
Review
Embryonic boundaries were first described in Drosophila, and then in vertebrate embryos, as cellular interfaces between compartments. They display signaling properties and in vertebrates might allocate cells fated to different anatomical structures, or cells that will play different functions over time. One of the vertebrate embryonic structures with boundaries is the hindbrain, the posterior brain vesicle, which is transitory segmented upon morphogenesis. The hindbrain is formed by iterative units called rhombomeres that constitute units of gene expression and cell-lineage compartments. Rhombomeric cells are segregated by interhombomeric boundaries, which are prefigured by sharp gene expression borders. Hindbrain boundaries were first described as static groups of cells. However, later discoveries demonstrated the dynamic behavior of this specific cell population. They play distinct functional properties during brain morphogenesis that partially overlap on time, starting as a mechanical barrier to prevent cell intermingling, becoming a signaling hub, to finally constitute a group of proliferating progenitors providing differentiated neurons to the system. In this review, I try to give a more functional overview of this segmentation process and in particular of hindbrain boundaries. I will discuss the new challenges in the field on how to integrate cell fate specification and morphogenesis during brain embryonic development.
Topics: Animals; Cell Proliferation; Embryonic Development; Humans; Mechanotransduction, Cellular; Models, Biological; Phylogeny; Rhombencephalon
PubMed: 32448645
DOI: 10.1016/j.semcdb.2020.05.002 -
Molecular Genetics and Metabolism 2003The cerebellum is the primary motor coordination center of the CNS and is also involved in cognitive processing and sensory discrimination. Multiple cerebellar... (Review)
Review
The cerebellum is the primary motor coordination center of the CNS and is also involved in cognitive processing and sensory discrimination. Multiple cerebellar malformations have been described in humans, however, their developmental and genetic etiologies currently remain largely unknown. In contrast, there is extensive literature describing cerebellar malformations in the mouse. During the past decade, analysis of both spontaneous and gene-targeted neurological mutant mice has provided significant insight into the molecular and cellular mechanisms that regulate cerebellar development. Cerebellar development occurs in several distinct but interconnected steps. These include the establishment of the cerebellar territory along anterior-posterior and dorsal-ventral axes of the embryo, initial specification of the cerebellar cell types, their subsequent proliferation, differentiation and migration, and, finally, the interconnection of the cerebellar circuitry. Our understanding of the basis of these developmental processes is certain to provide insight into the nature of human cerebellar malformations.
Topics: Animals; Cell Movement; Cerebellum; Gene Expression Regulation, Developmental; Humans; Mesencephalon; Mice; Mutation; Rhombencephalon
PubMed: 14567957
DOI: 10.1016/j.ymgme.2003.08.019 -
Respiratory Physiology & Neurobiology Nov 2019For many, if not all, air-breathing vertebrates, breathing-like movements begin while the embryo is still ensconced in an aqueous environment. This is because primordial... (Review)
Review
For many, if not all, air-breathing vertebrates, breathing-like movements begin while the embryo is still ensconced in an aqueous environment. This is because primordial regions of the CNS become spontaneously active during early gestation and then must functionally transform and specialize once air breathing commences. The degree to which the embryonic ventilatory control system is established and competent at birth is variable, however, even between different components of the respiratory system. Moreover, the embryological experiences of an individual can also affect the outcomes and responsiveness of ventilation to respiratory stimuli and these details have major clinical implications. The broad field of respiratory neurobiology still has much to learn about the ontogeny of breathing control systems, and the oviparity of birds provides a unique model to examine how early rhythms transform day-to-day as they become functional. This hybrid review and research article will highlight the contributions of birds to the study of breathing control during early development. We will detail what is currently known about the onset and maturation of respiratory rhythm generation and also provide novel data about the development of central chemosensitivity. Finally, we will review data regarding the development of peripheral afferent inputs during early development and discuss whole-animal reflex responsiveness to common respiratory stimuli, both chronic and acute, during the incubation period and following hatching.
Topics: Animals; Animals, Newborn; Birds; Embryo, Nonmammalian; Embryonic Development; Respiration; Rhombencephalon
PubMed: 31283998
DOI: 10.1016/j.resp.2019.06.003 -
Neuroscience Aug 2007Brainstem networks generating the respiratory rhythm in lampreys are still not fully characterized. In this study, we described the patterns of respiratory activities...
Brainstem networks generating the respiratory rhythm in lampreys are still not fully characterized. In this study, we described the patterns of respiratory activities and we identified the general location of underlying neural networks. In a semi-intact preparation including the brain and gills, rhythmic discharges were recorded bilaterally with surface electrodes placed over the vagal motoneurons. The main respiratory output driving rhythmic gill movements consisted of short bursts (40.9+/-15.6 ms) of discharge occurring at a frequency of 1.0+/-0.3 Hz. This fast pattern was interrupted by long bursts (506.3+/-174.6 ms) recurring with an average period of 37.4+/-24.9 s. After isolating the brainstem by cutting all cranial nerves, the frequency of the short respiratory bursts did not change significantly, but the slow pattern was less frequent. Local injections of a glutamate agonist (AMPA) and antagonists (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or D,L-amino-5-phosphonopentanoic acid (AP5)) were made over different brainstem regions to influence respiratory output. The results were similar in the semi-intact and isolated-brainstem preparations. Unilateral injection of AP5 or CNQX over a rostral rhombencephalic region, lateral to the rostral pole of the trigeminal motor nucleus, decreased the frequency of the fast respiratory rhythm bilaterally or stopped it altogether. Injection of AMPA at the same site increased the rate of the fast respiratory rhythm and decreased the frequency of the slow pattern. The activity recorded in this area was synchronous with that recorded over the vagal motoneurons. After a complete transverse lesion of the brainstem caudal to the trigeminal motor nucleus, the fast rhythm was confined to the rostral area, while only the slow activity persisted in the vagal motoneurons. Our results support the hypothesis that normal breathing depends on the activity of neurons located in the rostral rhombencephalon in lampreys, whereas the caudal rhombencephalon generates the slow pattern.
Topics: Action Potentials; Animals; Biological Clocks; Branchial Region; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Female; Gills; Glutamic Acid; Male; Medulla Oblongata; Motor Neurons; Muscle, Skeletal; Nerve Net; Neural Pathways; Periodicity; Petromyzon; Pons; Respiratory Center; Respiratory Physiological Phenomena; Rhombencephalon; Synaptic Transmission; Time Factors; Vagus Nerve
PubMed: 17618060
DOI: 10.1016/j.neuroscience.2007.05.023 -
The Lancet. Neurology Apr 2013Historically, the midbrain and hindbrain have been considered of secondary importance to the cerebrum, which has typically been acknowledged as the most important part... (Review)
Review
Historically, the midbrain and hindbrain have been considered of secondary importance to the cerebrum, which has typically been acknowledged as the most important part of the brain. In the past, radiologists and pathologists did not regularly examine these structures-also known as the brainstem and cerebellum-because they are small and difficult to remove without damage. With recent developments in neuroimaging, neuropathology, and neurogenetics, many developmental disorders of the midbrain and hindbrain have emerged as causes of neurodevelopmental dysfunction. These research advances may change the way in which we treat these patients in the future and will enhance the clinical acumen of the practising neurologist and thereby improve the diagnosis and treatment of these patients.
Topics: Animals; Diagnostic Imaging; Humans; Mesencephalon; Rhombencephalon
PubMed: 23518331
DOI: 10.1016/S1474-4422(13)70024-3 -
Developmental Biology Dec 2018Wilhelm His (1831-1904) provided lasting insights into the development of the central and peripheral nervous system using innovative technologies such as the microtome,... (Review)
Review
Wilhelm His (1831-1904) provided lasting insights into the development of the central and peripheral nervous system using innovative technologies such as the microtome, which he invented. 150 years after his resurrection of the classical germ layer theory of Wolff, von Baer and Remak, his description of the developmental origin of cranial and spinal ganglia from a distinct cell population, now known as the neural crest, has stood the test of time and more recently sparked tremendous advances regarding the molecular development of these important cells. In addition to his 1868 treatise on 'Zwischenstrang' (now neural crest), his work on the development of the human hindbrain published in 1890 provided novel ideas that more than 100 years later form the basis for penetrating molecular investigations of the regionalization of the hindbrain neural tube and of the migration and differentiation of its constituent neuron populations. In the first part of this review we briefly summarize the major discoveries of Wilhelm His and his impact on the field of embryology. In the second part we relate His' observations to current knowledge about the molecular underpinnings of hindbrain development and evolution. We conclude with the proposition, present already in rudimentary form in the writings of His, that a primordial spinal cord-like organization has been molecularly supplemented to generate hindbrain 'neomorphs' such as the cerebellum and the auditory and vestibular nuclei and their associated afferents and sensory organs.
Topics: Animals; Biological Evolution; Body Patterning; Cell Differentiation; Cerebellum; Ganglia, Spinal; Germ Layers; History, 17th Century; History, 18th Century; Humans; Neural Crest; Neural Tube; Neurons; Organogenesis; Rhombencephalon
PubMed: 29447907
DOI: 10.1016/j.ydbio.2018.02.001 -
Trends in Neurosciences Dec 2004The midbrain-hindbrain organizer (MHO) is a signalling centre that orchestrates development of the mesencephalic and anterior metencephalic primordia. In recent years,... (Review)
Review
The midbrain-hindbrain organizer (MHO) is a signalling centre that orchestrates development of the mesencephalic and anterior metencephalic primordia. In recent years, details have been revealed about the molecular nature of these signals, their transmission and reception, and the regulatory processes associated with MHO function. This article reviews recent progress in understanding the genetic and molecular components of the MHO, and how they synergize to control brain development.
Topics: Animals; Biological Evolution; Gene Expression Regulation, Developmental; Growth Substances; Mesencephalon; Morphogenesis; Neurons; Organizers, Embryonic; Rhombencephalon; Signal Transduction
PubMed: 15541513
DOI: 10.1016/j.tins.2004.10.003 -
The Journal of Comparative Neurology Mar 1987Short-survival thymidine radiograms from rat embryos aged 13-19 days were analyzed to delineate the precerebellar neuroepithelium of the rhombencephalon. The original...
Short-survival thymidine radiograms from rat embryos aged 13-19 days were analyzed to delineate the precerebellar neuroepithelium of the rhombencephalon. The original definition of the term "rhombencephalon" was modified to refer only to the unique dorsal portion (surface plate) of the medulla and pons where the neural groove fails to fuse and, instead, the medullary velum covers the rhomboid lumen of the fourth ventricle. Initially, the neuroepithelial tissue of the rhombencephalon consists of a pair of rostral and caudal bridgeheads: the former the primary neuroepithelium of the cerebellum and the latter the primary neuroepithelium of the octavo-precerebellar system. The spatial relationship between the cerebellar and precerebellar neuroepithelia soon changes as a result of ongoing morphogenetic events, such that the cerebellar primordium assumes a dorsal position and the precerebellar primordium a ventral position, and the distance between the two decreases. Concurrently the tela choroidea invaginates into the fourth ventricle and a secondary precerebellar neuroepithelium develops. The rostral portion of the secondary precerebellar neuroepithelium grows forward along the choroid plexus and forms the medial recess of the anterior fourth ventricle, while its caudal portion grows in the opposite direction beneath the medullary velum and forms the rostral wall of the posterior fourth ventricle. Evidence will be presented in the succeeding papers that the primary precerebellar neuroepithelium first generates the neurons of the inferior olive that migrate by a circumferential intramural (parenchymal) route to their destination. Next, the neurons of the lateral reticular and external cuneate nuclei are generated. These migrate by a posterior extramural (superficial) route and settle contralaterally. Subsequently, the primary precerebellar neuroepithelium produces the neurons of the nucleus reticularis tegmenti pontis and these form the anterior extramural migratory stream and settle ipsilaterally. Finally, the secondary precerebellar neuroepithelium produces the latest generated neurons of the basal pontine gray that follow the anterior extramural stream and settle ipsilaterally.
Topics: Animals; Autoradiography; Cerebellar Nuclei; Epithelium; Radiography; Rats; Rats, Inbred Strains; Rhombencephalon; Thymidine
PubMed: 3693594
DOI: 10.1002/cne.902570402 -
Cellular and Molecular Life Sciences :... Sep 2013The midbrain-hindbrain boundary (MHB) is a highly conserved vertebrate signalling centre, acting to pattern and establish neural identities within the brain. While the... (Review)
Review
The midbrain-hindbrain boundary (MHB) is a highly conserved vertebrate signalling centre, acting to pattern and establish neural identities within the brain. While the core signalling pathways regulating MHB formation have been well defined, novel genetic and mechanistic processes that interact with these core components are being uncovered, helping to further elucidate the complicated networks governing MHB specification, patterning and shaping. Although formation of the MHB organiser is traditionally thought of as comprising three stages, namely positioning, induction and maintenance, we propose that a fourth stage, morphogenesis, should be considered as an additional stage in MHB formation. This review will examine evidence for novel factors regulating the first three stages of MHB development and will explore the evidence for regulation of MHB morphogenesis by non-classical MHB-patterning genes.
Topics: Animals; Body Patterning; Gene Expression Regulation, Developmental; Humans; Mesencephalon; Mice; Models, Neurological; Morphogenesis; Rhombencephalon; Signal Transduction; Zebrafish
PubMed: 23307071
DOI: 10.1007/s00018-012-1240-x -
Development, Growth & Differentiation Apr 2012In the nervous system, there are hundreds to thousands of neuronal cell types that have morphologically, physiologically, and histochemically different characteristics... (Review)
Review
In the nervous system, there are hundreds to thousands of neuronal cell types that have morphologically, physiologically, and histochemically different characteristics and this diversity may enable us to elicit higher brain function. A better understanding of the molecular machinery by which neuron subtype specification occurs is thus one of the most important issues in brain science. The dorsal hindbrain, including the cerebellum, is a good model system to study this issue because a variety of types of neurons are produced from this region. Recently developed genetic lineage-tracing methods in addition to gene-transfer technologies have clarified a fate map of neurons produced from the dorsal hindbrain and accelerated our understanding of the molecular machinery of neuronal subtype specification in the nervous system.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Lineage; Cell Nucleus; Cerebellum; Embryo, Mammalian; Gene Expression Regulation, Developmental; Mice; Models, Neurological; Neuroepithelial Cells; Neurons; Protein Structure, Tertiary; Rhombencephalon
PubMed: 22404503
DOI: 10.1111/j.1440-169X.2012.01330.x