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The medial longitudinal fasciculus (MLF) is the first axon tract to develop in the ventral vertebrate brain. It originates in the diencephalon and projects caudally into the spinal cord, pioneering the path for later developing axons. Previous anatomical and expression analyses in the chicken suggested Semaphorin 3 A (Sema3A) as the candidate to repel the amniote MLF from the forebrain. However, studies in the zebrafish implicated a distantly related semaphorin with a role in axon fasciculation, not guidance. Thus, the mechanism accounting for the caudal projection of the MLF remains unclear. Here we show that misexpression of Sema3A or grafting of Sema3A-expressing cells into the path of the MLF diverts the axons or blocks their outgrowth in chicken embryos. In vitro, Sema3A exposure resulted in the collapse of MLF growth cones. A dominant-negative approach or siRNA to interfere with the function of the Sema3A receptor Neuropilin1 allowed MLF axons to project rostrally. Together, this suggests that Sema3a repulsion directs the caudal extension of the MLF to pioneer the ventral longitudinal tract. [Display omitted] • Sema3A is expressed rostral to the nucleus of the medial longitudinal fasciculus (MLF) prior to axon outgrowth. • Ectopic Sema3A diverts axons of the MLF. • Exposure to Sema3A causes growth cone collapse in MLF neurons. • Interfering with the semaphorin receptor Neuropilin1 allows randomisation of axon projection in theMLF. • These results indicate that Sema3A acts as a repellent to guide the MLF axons caudally. [ABSTRACT FROM AUTHOR]

Cross-correlation of magnetoencephalography (MEG) with time courses derived from the speech signal has shown differences in phase-locking between blind subjects able to comprehend accelerated speech and sighted controls. The present training study contributes to disentangle the effects of blindness and training. Both subject groups (baseline: n = 16 blind, 13 sighted; trained: 10 blind, 3 sighted) were able to enhance speech comprehension up to ca. 18 syllables per second. MEG responses phase-locked to syllable onsets were captured in five pre-defined source locations comprising left and right auditory cortex (A1), right visual cortex (V1), left inferior frontal gyrus (IFG) and left pre-supplementary motor area. Phase locking in A1 was consistently increased while V1 showed opposite training effects in blind and sighted subjects. Also the IFG showed some group differences indicating enhanced top-down strategies in sighted subjects while blind subjects may have a more fine-grained bottom-up resolution for accelerated speech. [ABSTRACT FROM AUTHOR]

Abstract: Blind people can learn to understand speech at ultra-high syllable rates (ca. 20syllables/s), a capability associated with hemodynamic activation of the central-visual system. To further elucidate the neural mechanisms underlying this skill, magnetoencephalographic (MEG) measurements during listening to sentence utterances were cross-correlated with time courses derived from the speech signal (envelope, syllable onsets and pitch periodicity) to capture phase-locked MEG components (14 blind, 12 sighted subjects; speech rate=8 or 16syllables/s, pre-defined source regions: auditory and visual cortex, inferior frontal gyrus). Blind individuals showed stronger phase locking in auditory cortex than sighted controls, and right-hemisphere visual cortex activity correlated with syllable onsets in case of ultra-fast speech. Furthermore, inferior-frontal MEG components time-locked to pitch periodicity displayed opposite lateralization effects in sighted (towards right hemisphere) and blind subjects (left). Thus, ultra-fast speech comprehension in blind individuals appears associated with changes in early signal-related processing mechanisms both within and outside the central-auditory terrain. [Copyright &y& Elsevier]

Discourse structures enable us to generate expectations based upon linguistic material that has already been introduced. We investigated how the required cognitive operations such as reference processing, identification of critical items, and eventual handling of violations correlate with neuronal activity within the language network of the brain. To this end, we conducted a functional magnetic resonance imaging (fMRI) study in which we manipulated spoken discourse coherence by using presuppositions (PSPs) that either correspond or fail to correspond to items in preceding context sentences. Definite and indefinite determiners were used as PSP triggers, referring to (non-) uniqueness or (non-) existence of an item. Discourse adequacy was tested by means of a behavioral rating during fMRI. Discourse violations yielded bilateral hemodynamic activation within the inferior frontal gyrus (IFG), the inferior parietal lobe including the angular gyrus (IPL/AG), the pre-supplementary motor area (pre-SMA), and the basal ganglia (BG). These findings illuminate cognitive aspects of PSP processing: (1) a reference process requiring working memory (IFG), (2) retrieval and integration of semantic/pragmatic information (IPL/AG), (3) cognitive control of inconsistency management (pre-SMA/BG) in terms of "successful" comprehension despite PSP violations at the surface. These results provide the first fMRI evidence needed to develop a functional neuroanatomical model for context-dependent sentence comprehension based on the example of PSP processing. [ABSTRACT FROM AUTHOR]

The vertebrate head mesoderm provides the heart, the great vessels, some smooth and most head skeletal muscle, in addition to parts of the skull. It has been speculated that the ability to generate cardiac and smooth muscle is the evolutionary ground-state of the tissue. However, whether indeed the entire head mesoderm has generic cardiac competence, how long this may last, and what happens as cardiac competence fades, is not clear. Bone morphogenetic proteins (Bmps) are known to promote cardiogenesis. Using 41 different marker genes in the chicken embryo, we show that the paraxial head mesoderm that normally does not engage in cardiogenesis has the ability to respond to Bmp for a long time. However, Bmp signals are interpreted differently at different time points. Up to early head fold stages, the paraxial head mesoderm is able to read Bmps as signal to engage in the cardiac programme; the ability to upregulate smooth muscle markers is retained slightly longer. Notably, as cardiac competence fades, Bmp promotes the head skeletal muscle programme instead. The switch from cardiac to skeletal muscle competence is Wnt-independent as Wnt caudalises the head mesoderm and also suppresses Msc-inducing Bmp provided by the prechordal plate, thus suppressing both the cardiac and the head skeletal muscle programmes. Our study for the first time suggests a specific transition state in the embryo when cardiac competence is replaced by skeletal muscle competence. It sets the stage to unravel the cardiac-skeletal muscle antagonism that is known to partially collapse in heart failure. [Display omitted] • The early chicken paraxial head mesoderm has cardiac and smooth muscle competence. • Cardiac competence fades after HH5/6, smooth muscle competence after HH9/10. • From HH7/8 onwards, Bmp promotes the head skeletal muscle programme. • Wnt caudalises the head mesoderm, in part by removing protection from Retinoic Acid. • Wnt suppresses Bmp-signalling from the prechordal plate. Summary statement: The head mesoderm has generic cardiac competence until early head fold stages. Thereafter, cardiac competence fades in the paraxial region, and Bmp promotes head skeletal muscle programmes instead of cardiac programmes. [ABSTRACT FROM AUTHOR]

Craniofacial muscles, muscles that move the eyes, control facial expression and allow food uptake and speech, have long been regarded as a variation on the general body muscle scheme. However, evidence has accumulated that the function of head muscles, their developmental anatomy and the underlying regulatory cascades are distinct. This article reviews the key aspects of craniofacial muscle and muscle stem cell formation and discusses how this differs from the trunk programme of myogenesis; we show novel RNAseq data to support this notion. We also trace the origin of head muscle in the chordate ancestors of vertebrates and discuss links with smooth-type muscle in the primitive chordate pharynx. We look out as to how the special properties of head muscle precursor and stem cells, in particular their competence to contribute to the heart, could be exploited in regenerative medicine. [ABSTRACT FROM AUTHOR]

Chordates are characterised by contractile muscle on either side of the body that promotes movement by side-to-side undulation. In the lineage leading to modern jawed vertebrates (crown group gnathostomes), this system was refined: body muscle became segregated into distinct dorsal (epaxial) and ventral (hypaxial) components that are separately innervated by the medial and hypaxial motors column, respectively, via the dorsal and ventral ramus of the spinal nerves. This allows full three-dimensional mobility, which in turn was a key factor in their evolutionary success. How the new gnathostome system is established during embryogenesis and how it may have evolved in the ancestors of modern vertebrates is not known. Vertebrate Engrailed genes have a peculiar expression pattern as they temporarily demarcate a central domain of the developing musculature at the epaxial-hypaxial boundary. Moreover, they are the only genes known with this particular expression pattern. The aim of this study was to investigate whether Engrailed genes control epaxial-hypaxial muscle development and innervation. Investigating chick, mouse and zebrafish as major gnathostome model organisms, we found that the Engrailed expression domain was associated with the establishment of the epaxial-hypaxial boundary of muscle in all three species. Moreover, the outgrowing epaxial and hypaxial nerves orientated themselves with respect to this Engrailed domain. In the chicken, loss and gain of Engrailed function changed epaxial-hypaxial somite patterning. Importantly, in all animals studied, loss and gain of Engrailed function severely disrupted the pathfinding of the spinal motor axons, suggesting that Engrailed plays an evolutionarily conserved role in the separate innervation of vertebrate epaxial-hypaxial muscle. [ABSTRACT FROM AUTHOR]

Abstract: The vertebrate head–trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head–trunk interface. [Copyright &y& Elsevier]

In all jaw-bearing vertebrates, three-dimensional mobility relies on segregated, separately innervated epaxial and hypaxial skeletal muscles. In amniotes, these muscles form from the morphologically continuous dermomyotome and myotome, whose epaxial–hypaxial subdivision and hence the formation of distinct epaxial–hypaxial muscles is not understood.Here we show that En1 expression labels a central subdomain of the avian dermomyotome, medially abutting the expression domain of the lead-lateral or hypaxial marker Sim1. En1 expression is maintained when cells from the En1-positive dermomyotome enter the myotome and dermatome, thereby superimposing the En1–Sim1 expression boundary onto the developing musculature and dermis.En1 cells originate from the dorsomedial edge of the somite. Their development is under positive control by notochord and floor plate (Shh), dorsal neural tube (Wnt1) and surface ectoderm (Wnt1-like signalling activity) but negatively regulated by the lateral plate mesoderm (BMP4). This dependence on epaxial signals and suppression by hypaxial signals places En1 into the epaxial somitic programme. Consequently, the En1–Sim1 expression boundary marks the epaxial–hypaxial dermomyotomal or myotomal boundary.In cell aggregation assays, En1- and Sim1-expressing cells sort out, suggesting that the En1–Sim1 expression boundary may represent a true compartment boundary, foreshadowing the epaxial–hypaxial segregation of muscle. [Copyright &y& Elsevier]