Authors: M Lettau, R D Munk, S Munk-Schulenburg...

Topics: Abnormalities, Multiple; Alopecia; Brain; Cerebellum; Child; Craniofacial Abnormalities; Diagnosis, Differential; Female; Growth Disorders; Humans; Neurocutaneous Syndromes; Rhombencephalon

PubMed: 23494500
DOI: 10.1055/s-0033-1335027

Review

Authors: Keith T Sillar

Topics: Animals; Biological Evolution; Fishes; Neurons; Reflex, Startle; Rhombencephalon; Synaptic Transmission

PubMed: 19439253
DOI: 10.1016/j.cub.2009.02.025

Authors: Arie Horowitz, Michael Simons

Tubular structures are a fundamental anatomical theme recurring in a wide range of animal species. In mammals, tubulogenesis underscores the development of several systems and organs, including the vascular system, the lungs, and the kidneys. All tubular systems are hierarchical, branching into segments of gradually diminishing diameter. There are only two cell types that form the lumen of tubular systems – either endothelial cells in the vascular system, or epithelial cells in all other organs. The most important feature in determining the morphology of the tubular systems is the frequency and geometry of branching. Hence, deciphering the molecular mechanisms underlying the sprouting of new branches from pre-existing ones is the key to understanding the formation of tubular systems. The morphological similarity between the various tubular systems is underscored by similarities between the signaling pathways which control their branching. A prominent feature common to these pathways is their duality – an agonist counterbalanced by an inhibitor. The formation of the tracheal system in is driven by fibroblast growth factor (FGF) and inhibited by Sprouty/Notch. In vertebrates, the analogous pathways are FGF and transforming growth factor β in epithelial tubular systems, or vascular endothelial growth factor and Notch in the vascular system.

Topics: Animals; Blood Vessels; Cell Movement; Cell Proliferation; Endothelial Cells; Mice; Morphogenesis; Neovascularization, Physiologic; Protein Isoforms; Proteoglycans; Rhombencephalon; Vascular Endothelial Growth Factor A

PubMed: 19179661
DOI: 10.1161/CIRCRESAHA.108.191494

Review

Authors: Robb Krumlauf, David G Wilkinson

During early development, the hindbrain is sub-divided into rhombomeres that underlie the organisation of neurons and adjacent craniofacial tissues. A gene regulatory network of signals and transcription factors establish and pattern segments with a distinct anteroposterior identity. Initially, the borders of segmental gene expression are imprecise, but then become sharply defined, and specialised boundary cells form. In this Review, we summarise key aspects of the conserved regulatory cascade that underlies the formation of hindbrain segments. We describe how the pattern is sharpened and stabilised through the dynamic regulation of cell identity, acting in parallel with cell segregation. Finally, we discuss evidence that boundary cells have roles in local patterning, and act as a site of neurogenesis within the hindbrain.

Topics: Animals; Body Patterning; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Rhombencephalon; Vertebrates

PubMed: 34323269
DOI: 10.1242/dev.186460

Review

Authors: Véronique Dubreuil, Jacques Barhanin, Christo Goridis...

In the last few years, elucidation of the architecture of breathing control centres has reached the cellular level. This has been facilitated by increasing knowledge of the molecular signatures of various classes of hindbrain neurons. Here, we review the advances achieved by studying the homeodomain factor Phox2b, a transcriptional determinant of neuronal identity in the central and peripheral nervous systems. Evidence from human genetics, neurophysiology and mouse reverse genetics converges to implicate a small population of Phox2b-dependent neurons, located in the retrotrapezoid nucleus, in the detection of CO(2), which is a paramount source of the 'drive to breathe'. Moreover, the same and other studies suggest that an overlapping or identical neuronal population, the parafacial respiratory group, might contribute to the respiratory rhythm at least in some circumstances, such as for the initiation of breathing following birth. Together with the previously established Phox2b dependency of other respiratory neurons (which we review briefly here), our new data highlight a key role of this transcription factor in setting up the circuits for breathing automaticity.

Topics: Animals; Carbon Dioxide; Homeodomain Proteins; Humans; Hypoventilation; Mice; Mutation; Neurons; Respiratory Mechanics; Rhombencephalon; Transcription Factors

PubMed: 19651649
DOI: 10.1098/rstb.2009.0085

Review

Authors: Kimberly A Aldinger, Jennifer C Dempsey, Hannah M Tully...

Rhombencephalosynapsis (RES) is a unique cerebellar malformation characterized by fusion of the cerebellar hemispheres with partial or complete absence of a recognizable cerebellar vermis. Subsets of patients also have other brain malformations such as midbrain fusion with aqueductal stenosis, characteristic craniofacial features (prominent forehead, flat midface, hypertelorism, ear abnormalities), and somatic malformations (heart, kidney, spine, and limb defects). Similar to known genetic brain malformations, the RES cerebellar malformation is highly stereotyped, yet no genetic causes have been identified. Here, we outline our current understanding of the genetic basis for RES, discuss limitations, and outline future approaches to identifying the causes of this fascinating brain malformation.

Topics: Cerebellar Diseases; Cerebellum; Growth Disorders; Humans; Rhombencephalon

PubMed: 30580482
DOI: 10.1002/ajmg.c.31666

Review

Authors: Richard C Rogers, Gerlinda E Hermann

Hindbrain astrocytes are emerging as critical components in the regulation of homeostatic functions by either modulating synaptic activity or serving as primary detectors of physiological parameters. Recent studies have suggested that the glucose counter-regulation response (CRR), a critical defense against hypoglycemic emergencies, is dependent on glucoprivation-sensitive astrocytes in the hindbrain. This subpopulation of astrocytes produces a robust calcium signal in response to glucopenic stimuli. Both ex vivo and in vivo evidence suggest that low-glucose sensitive astrocytes utilize purinergic gliotransmission to activate catecholamine neurons in the hindbrain that are critical to the generation of the integrated CRR. Lastly, reports in the clinical literature suggest that an uncontrolled activation of CRR may as part of the pathology of severe traumatic injury. Work in our laboratory also suggests that this pathological hyperglycemia resulting from traumatic injury may be caused by the action of thrombin (generated by tissue trauma or bleeding) on hindbrain astrocytes. Similar to their glucopenia-sensitive neighbors, these hindbrain astrocytes may trigger hyperglycemic responses by their interactions with catecholaminergic neurons.

Topics: Animals; Astrocytes; Glucose; Homeostasis; Humans; Metabolism; Rhombencephalon

PubMed: 30797812
DOI: 10.1016/j.physbeh.2019.02.025

Review

Authors: David G Wilkinson

Studies of the vertebrate hindbrain have revealed parallel mechanisms that establish sharp segments with a distinct and homogeneous regional identity. Recent work has revealed roles of cell identity regulation and its relationships with cell segregation. At early stages, there is overlapping expression at segment borders of the Egr2 and Hoxb1 transcription factors that specify distinct identities, which is resolved by reciprocal repression. Computer simulations show that this dynamic regulation of cell identity synergises with cell segregation to generate sharp borders. Some intermingling between segments occurs at early stages, and ectopic egr2-expressing cells switch identity to match their new neighbours. This switching is mediated by coupling between egr2 expression and the level of retinoic acid signalling, which acts in a community effect to maintain homogeneous segmental identity. These findings reveal an interplay between cell segregation and the dynamic regulation of cell identity in the formation of sharp patterns in the hindbrain and raise the question of whether similar mechanisms occur in other tissues.

Topics: Animals; Cell Separation; Humans; Rhombencephalon

PubMed: 30135723
DOI: 10.12688/f1000research.15391.1

Review

Authors: Angelo Iulianella, Richard J Wingate, Cecilia B Moens...

The cerebellum coordinates vestibular input into the hindbrain to control balance and movement, and its anatomical complexity is increasingly viewed as a high-throughput processing center for sensory and cognitive functions. Cerebellum development however is relatively simple, and arises from a specialized structure in the anterior hindbrain called the rhombic lip, which along with the ventricular zone of the rostral-most dorsal hindbrain region, give rise to the distinct cell types that constitute the cerebellum. Granule cells, being the most numerous cell types, arise from the rhombic lip and form a dense and distinct layer of the cerebellar cortex. In this short review, we describe the various strategies used by amniotes and anamniotes to generate and diversify granule cell types during cerebellar development.

Topics: Animals; Cell Differentiation; Cerebellum; Humans; Neocortex; Rhombencephalon

PubMed: 31131952
DOI: 10.1002/dvdy.64

Review

Authors: Darcy B Kelley, Taffeta M Elliott, Ben J Evans...

The vertebrate hindbrain includes neural circuits that govern essential functions including breathing, blood pressure and heart rate. Hindbrain circuits also participate in generating rhythmic motor patterns for vocalization. In most tetrapods, sound production is powered by expiration and the circuitry underlying vocalization and respiration must be linked. Perception and arousal are also linked; acoustic features of social communication sounds-for example, a baby's cry-can drive autonomic responses. The close links between autonomic functions that are essential for life and vocal expression have been a major in vivo experimental challenge. Xenopus provides an opportunity to address this challenge using an ex vivo preparation: an isolated brain that generates vocal and breathing patterns. The isolated brain allows identification and manipulation of hindbrain vocal circuits as well as their activation by forebrain circuits that receive sensory input, initiate motor patterns and control arousal. Advances in imaging technologies, coupled to the production of Xenopus lines expressing genetically encoded calcium sensors, provide powerful tools for imaging neuronal patterns in the entire fictively behaving brain, a goal of the BRAIN Initiative. Comparisons of neural circuit activity across species (comparative neuromics) with distinctive vocal patterns can identify conserved features, and thereby reveal essential functional components.

Topics: Animals; Exhalation; Organ Culture Techniques; Prosencephalon; Rhombencephalon; Vocalization, Animal; Xenopus laevis

PubMed: 28095617
DOI: 10.1002/dvg.22999