Initiation of facial motoneurone migration is dependent on rhombomeres 5 and 6

Development ◽  
2001 ◽  
Vol 128 (19) ◽  
pp. 3707-3716
Author(s):  
Michèle Studer

In mammals, facial branchiomotor (FBM) neurones are born in ventral rhombomere (r) 4 and migrate through r5 to dorsal r6 where they form the facial motor nucleus. This pattern of migration gives rise to the distinctive appearance of the internal genu of the facial nerve, which is lacking in birds. To distinguish between extrinsic cues and intrinsic factors in the caudal migration of FBM neurones, this study takes advantage of the evolutionary migratory difference between mouse and chick in generating mouse-chick chimaeras in ovo. After the homotopic transplantation of mouse r5 and/or r6 into a chick embryo, chick ventral r4 neurones redirected their cell bodies towards the ectopic mouse source and followed a caudal migratory path, reminiscent of mouse FBM neurones. In a second series of grafting experiments, when mouse r4 was transplanted in place of chick r4, mouse r4 neurones were unable to migrate into chick r5, although mouse and chick cells were able to mix freely within r4. Thus, these data suggest that local environmental cues embedded in mouse r5 and r6 are directly involved in initiating caudal migration of FBM neurones. In addition, they demonstrate that chick FBM neurones are competent to recapitulate a migratory behaviour that has been lost during avian phylogeny.

1987 ◽  
Vol 132 (1) ◽  
pp. 111-131
Author(s):  
M. E. Spira ◽  
D. Zeldes ◽  
B. Hochner ◽  
A. Dormann

Severed adult neurones, which are capable of regrowth, encounter different microenvironments from those encountered during development. Moreover, adult neurones may respond in a different manner from developing neurones to the same environmental cues. Thus, the recovery of the integrative and transmission capabilities (which depend on the neuronal architecture, passive and active membrane properties, and synaptic receptor distribution) by a regenerating adult neurone may not be complete. In the present review, we examine several aspects of the outcome of the interaction between the microenvironment and regrowing neurones using the cockroach giant interneurones (GINs) as a model system. We demonstrate that whereas extrinsic cues govern the morphological redifferentiation and distribution of synaptic receptors, the distribution of voltage-dependent Ca2+ channels is to a large extent determined by intrinsic factors. The pathway of regrowth and the architecture of regenerating GINs were studied by examination of intracellularly stained fibres. The environments provided by the connectives and ganglia are different. The elongating sprouts in the connective appeared as smooth cylinders. Within the ganglionic domain, the main longitudinal sprouts emitted neurites which extended and branched into the neuropile. The local cues for branching of neurites were eliminated by freezing and thawing of the ganglia prior to the arrival of the growing tips. The failure to extend neurites under these conditions is attributed to the elimination of extrinsic signals for morphological redifferentiation of the fibres, since the same fibres emit neurites in anterior ganglia which have not been subjected to freezing and thawing. The distribution of acetylcholine receptors (AChRs) on the GINs was mapped by ionophoretic application of ACh. In both the intact and regenerating GINs receptors were located only on the neurites. Freezing and thawing of a ganglion eliminated the local signals for insertion and/or activation of AChRs on the neurites. Thus, both the morphological redifferentiation and the distribution of AChRs are affected by the microenvironment. Voltage-dependent Ca2+ channels were detected after intracellular injection of tetraethylammonium into the GIN and in the presence of tetrodotoxin (TTX) and Ba2+ in the extracellular space. The regrowing axon tips always revealed large barium action potentials independent of the CNS microenvironment. This observation is consistent with the hypothesis that Ca2+ plays an important role in the growth process. However, increased Ba2+ responsiveness was also observed in axonal segments proximal to the region of neuronal extension.(ABSTRACT TRUNCATED AT 400 WORDS)


2021 ◽  
Vol 218 (8) ◽  
Author(s):  
Xinying Zong ◽  
Xiaolei Hao ◽  
Beisi Xu ◽  
Jeremy Chase Crawford ◽  
Shaela Wright ◽  
...  

T reg cells bearing a diverse antigen receptor repertoire suppress pathogenic T cells and maintain immune homeostasis during their long lifespan. How their robust function is determined genetically remains elusive. Here, we investigate the regulatory space of the cis-regulatory elements of T reg lineage–specifying factor Foxp3. Foxp3 enhancers are known as distinct readers of environmental cues controlling T reg cell induction or lineage stability. However, their single deficiencies cause mild, if any, immune dysregulation, leaving the key transcriptional mechanisms determining Foxp3 expression and thereby T reg cell suppressive capacity uncertain. We examined the collective activities of Foxp3 enhancers and found that they coordinate to maximize T reg cell induction, Foxp3 expression level, or lineage stability through distinct modes and that ablation of synergistic enhancers leads to lethal autoimmunity in young mice. Thus, the induction and maintenance of a diverse, stable T reg cell repertoire rely on combinatorial Foxp3 enhancers, suggesting broad, stage-specific, synergistic activities of cell-intrinsic factors and cell-extrinsic cues in determining T reg cell suppressive capacity.


Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 388-399 ◽  
Author(s):  
Youli Hu ◽  
Subathra Poopalasundaram ◽  
Anthony Graham ◽  
Pierre-Marc Bouloux

Fibroblast growth factor (FGF) signaling is essential for both olfactory bulb (OB) morphogenesis and the specification, migration, and maturation of the GnRH-secreting neurons. Disruption of FGF signaling contributes to Kallmann syndrome characterized by both anosmia and sexual immaturity. However, several unanswered questions remain as to which specific FGF receptor (FGFR)-1 signaling pathways are necessary for OB and GnRH neuronal development. Here, using pharmacological phosphatidylinositol 3-kinase (PI3K) isoform-specific inhibitors, we demonstrate a central role for the PI3K p110α isoform as a downstream effector of FGFR1 signaling for both GnRH neuronal migration and OB development. We show that signaling via the PI3K p110α isoform is required for GnRH neuronal migration in explant cultures of embryonic day (E) 4 chick olfactory placodes. We also show that in ovo administration of LY294002, a global PI3K inhibitor as well as an inhibitor to the PI3K p110α isoform into the olfactory placode of E3 chick embryo impairs GnRH neuronal migration toward the forebrain. In contrast, in ovo PI3K inhibitor treatment produced no obvious defects on primary olfactory sensory neuron axonal targeting and bundle formation. We also demonstrate that anosmin-1 and FGF2 induced neuronal migration of immortalized human embryonic GnRH neuroblast cells (FNC-B4-hTERT) is mediated by modulating FGFR1 signaling via the PI3K p110α isoform, specifically through phosphorylation of the PI3K downstream effectors, Akt and glycogen synthase kinase-3β. Finally, we show that neurite outgrowth and elongation of OB neurons in E10 chick OB explants are also dependent on the PI3K p110α isoform downstream of FGFR1. This study provides mechanistic insight into the etiology of Kallmann syndrome.


Development ◽  
1992 ◽  
Vol 114 (3) ◽  
pp. 729-741 ◽  
Author(s):  
K.G. Storey ◽  
J.M. Crossley ◽  
E.M. De Robertis ◽  
W.E. Norris ◽  
C.D. Stern

Induction and regionalisation of the chick nervous system were investigated by transplanting Hensen's node into the extra-embryonic region (area opaca margin) of a host embryo. Chick/quail chimaeras were used to determine the contributions of host and donor tissue to the supernumerary axis, and three molecular markers, Engrailed, neurofilaments (antibody 3A10) and XlHbox1/Hox3.3 were used to aid the identification of particular regions of the ectopic axis. We find that the age of the node determines the regions of the nervous system that form: young nodes (stages 2–4) induced both anterior and posterior nervous system, while older nodes (stages 5–6) have reduced inducing ability and generate only posterior nervous system. By varying the age of the host embryo, we show that the competence of the epiblast to respond to neural induction declines after stage 4. We conclude that during normal development, the initial steps of neural induction take place before stage 4 and that anteroposterior regionalisation of the nervous system may be a later process, perhaps associated with the differentiating notochord. We also speculate that the mechanisms responsible for induction of head CNS differ from those that generate the spinal cord: the trunk CNS could arise by homeogenetic induction by anterior CNS or by elongation of neural primordia that are induced very early.


Development ◽  
1986 ◽  
Vol 95 (1) ◽  
pp. 147-168
Author(s):  
Jane Butler ◽  
Peter Cauwenbergs ◽  
Ethel Cosmos

The extent of interaction between brachial muscles and foreign (thoracic) nerves of the chick embryo was determined during an extended period of development in ovo from the perspectives of innervation pattern, function (motility analyses), muscle growth (quantitative analyses of muscle volume) and fibre-type expression (myosin-ATPase profiles). Results indicated that according to all parameters analysed, initially a compatible union existed between the foreign nerves and their muscle targets. During subsequent stages of development, deterioration of the once compatible relationship emerged, until eventually denervation of muscles, i.e. an actual loss of intramuscular nerve branches, was observed. The process of denervation, which proceeded at a differential rate among individual muscles, however was restricted to brachial muscles derived from the premuscle masses of the wing bud. In contrast, brachial muscles of myotomal origin were spared the fate of wing-bud-derived muscles and maintained a successful union with the foreign nerves.


1987 ◽  
Vol 58 (3) ◽  
pp. 496-509 ◽  
Author(s):  
A. Lev-Tov ◽  
M. Tal

The structure and activity patterns of the anterior and posterior heads of the guinea pig digastric muscle (DG) were studied in ketamine-anesthetized guinea pigs. Collagen staining of longitudinal and transverse sections of the muscle revealed that the guinea pig DG is comprised of a unicompartmental anterior head (ADG) and a multicompartmental posterior head (PDG). The two heads are separated by a thin tendinous inscription that, unlike the intermediate tendon of the DG in humans, is not attached to the hyoid bone. The motor nuclei of the guinea pig DG were reconstructed using retrograde labeling with horseradish peroxidase. The motoneurons of the ADG were clustered in a longitudinal column within the trigeminal motor nucleus. The motoneurons of the PDG were segregated into two clusters within the facial motor nucleus. The cross-sectional areas of the ADG and PDG motoneuron somata exhibited unimodal frequency distributions and the average soma area was larger for ADG than PDG motoneurons. Histochemical characterization of ADG and PDG revealed that the two muscle heads contained the three main histochemical types of muscle fibers identified in limb muscles. The frequency distribution of fiber types in ADG and PDG were not significantly different. Both muscle heads were predominantly fast with slow oxidative fibers accounting for only 1.1 and 0.3% of the fibers in narrow dorsal regions of ADG and PDG, respectively, and 13.6 and 12.9% in the more ventral regions of ADG and PDG, respectively. Simultaneous recordings of EMGs from the ADG and PDG were carried out during spontaneously occurring rhythmical jaw movements. These recordings revealed a high degree of synchrony between the activities of the two heads, although differences were observed in the onset and duration of the EMG bursts. Activity in the PDG preceded activity in the ADG in most of the rhythmical cycles and persisted longer. The differences in latencies of time-locked EMGs evoked in the ADG and PDG by four-pulse cortical stimulation were much smaller than those observed between the activity bursts of the two heads during rhythmical jaw movements. It is suggested that the early activity in the PDG is accounted for by shorter central conduction times in the pathways onto it and/or by higher recruitability of its motor units. The early activity in PDG may serve to optimize the location of ADG on its length-tension curve prior to and during the active state.


2005 ◽  
Vol 66 (1) ◽  
pp. 22-34 ◽  
Author(s):  
Christopher D. Marshall ◽  
Ron H. Hsu ◽  
Susan W. Herring

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