Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1063-1075 ◽  
Author(s):  
E.M. Carpenter ◽  
J.M. Goddard ◽  
O. Chisaka ◽  
N.R. Manley ◽  
M.R. Capecchi

Targeted disruption of the murine hox-A1 gene results in severe defects in the formation of the hindbrain and associated cranial ganglia and nerves. Carbocyanine dye injections were used to trace afferent and efferent projections to and from the hindbrain in hox-A1-/hox-A1- mutant mice. Defects were observed in the position of efferent neurons in the hindbrain and in their projection patterns. In situ hybridization was used to analyze the transcription pattern of genes expressed within specific rhombomeres. Krox-20, int-2 (fgf-3), and hox-B1 all display aberrant patterns of expression in hox-A1- mutant embryos. The observed morphological and molecular defects suggest that there are changes in the formation of the hindbrain extending from rhombomere 3 through rhombomere 8 including the absence of rhombomere 5. Also, motor neurons identified by their axon projection patterns which would normally be present in the missing rhombomere appear to be respecified to or migrate into adjacent rhombomeres, suggesting a role for hox-A1 in the specification of cell identity and/or cell migration in the hindbrain.

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 290-OR
Author(s):  
NOEMI BRUSCO ◽  
GUIDO SEBASTIANI ◽  
GIADA LICATA ◽  
GIUSEPPINA E. GRIECO ◽  
GIANFRANCO DI GIUSEPPE ◽  
...  

2019 ◽  
Author(s):  
Michael C. Chiang ◽  
Eileen K. Nguyen ◽  
Andrew E. Papale ◽  
Sarah E. Ross

ABSTRACTThe lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents for diverse nocifensive responses have remained largely uncharacterized. Here, we show that two populations of efferent neurons from different regions of the lPBN collateralize to distinct targets. Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drive escape behaviors, whereas the activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin expressing neurons span cytoarchitecturally distinct domains of the lPBN to coordinate these distinct aspects of the nocifensive response.HIGHLIGHTSSpatially segregated neurons in the lPBN collateralize to distinct targets.Distinct output pathways give rise to separate aspects of the pain response.Dynorphin neurons within the lPBN convey noxious information across subdivisions.eTOC BLURBChiang et al. reveal that neurons in spatially segregated regions of the lateral parabrachial nucleus collateralize to distinct targets, and that activation of distinct efferents gives rise to separate components of the nocifensive response.


Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3575-3586 ◽  
Author(s):  
D. Meyer ◽  
T. Yamaai ◽  
A. Garratt ◽  
E. Riethmacher-Sonnenberg ◽  
D. Kane ◽  
...  

Neuregulin (also known as NDF, heregulin, ARIA, GGF or SMDF), induces cell growth and differentiation. Biological effects of neuregulin are mediated by members of the erbB family of tyrosine kinase receptors. Three major neuregulin isoforms are produced from the gene, which differ substantially in sequence and in overall structure. Here we use in situ hybridization with isoform-specific probes to illustrate the spatially distinct patterns of expression of the isoforms during mouse development. Ablation of the neuregulin gene in the mouse has demonstrated multiple and independent functions of this factor in development of both the nervous system and the heart. We show here that targeted mutations that affect different isoforms result in distinct phenotypes, demonstrating that isoforms can take over specific functions in vivo. Type I neuregulin is required for generation of neural crest-derived neurons in cranial ganglia and for trabeculation of the heart ventricle, whereas type III neuregulin plays an important role in the early development of Schwann cells. The complexity of neuregulin functions in development is therefore due to independent roles played by distinct isoforms.


1990 ◽  
Vol 153 (1) ◽  
pp. 1-10 ◽  
Author(s):  
CATHERINE MAGILL-SOLC ◽  
U. J. MCMAHAN

Several lies of evidence indicate that agrin, or a protein very similar to it, directs the formation and maintenance of the postsynaptic apparatus at the neuromuscular junction. We discuss the results of studies involving immunohistochemical, biochemical and in situ hybridization techniques that support hypothesis that agrin or agrin—like molecules active at the junction are produced bymotor neurons.


1984 ◽  
Vol 247 (6) ◽  
pp. E827-E832 ◽  
Author(s):  
D. L. Curry

The in situ brain-pancreas experimental model was used to investigate the influence of the vagus nerve during tonic direct central nervous system (CNS) inhibition of insulin secretion. Tonic CNS inhibition of insulin secretion was partially and transiently reversed following bilateral cervical vagotomy, suggesting that this inhibition includes a vagally mediated component. However, a substantial CNS inhibition of insulin secretion still occurred in the vagotomized preparations. This demonstrates that a major component producing tonic CNS inhibition of insulin secretion is independent of the vagus nerve and, furthermore, that it must be via direct sympathetic efferent pathways to the pancreas (because these preparations are functionally parasympathectomized via vagotomy). Further investigation into the vagus nerve involvement was carried out by stimulating either the afferent (central) or efferent (pancreatic) cut end of the vagus nerve of bilaterally vagotomized brain-pancreas preparations. Stimulation of the efferent vagus did not appreciably alter the effect of vagotomy on insulin secretion. However, when the central cut vagus was stimulated, the early transient reversal of tonic inhibition, which occurred in the vagotomized preparations, was totally reversed. This suggests that the vagally mediated early transient component of tonic CNS inhibition of insulin secretion is via afferent (central) neurons in the vagus nerve. These data demonstrate a reflex pathway for inhibition of insulin secretion that is comprised of vagal afferent neurons, the CNS, and sympathetic efferent neurons ending directly on the islets of Langerhans. It is tempting to speculate that gastrointestinal receptors exist that are capable of initiating this reflex inhibition of insulin secretion.


2000 ◽  
Vol 28 (6) ◽  
pp. 855-856 ◽  
Author(s):  
J. Edqvist ◽  
I. Farbos

In Euphorbia lagascae the major fatty acid in triacylglycerol is the epoxidated fatty acid vernolic acid (cis- 12-epoxyoctadeca-cis-9-enoic acid). The enzymic reactions occurring during the catabolism of epoxidated fatty acids during germination are not known, but it seems likely that the degradation requires the activity of an epoxide hydrolase. Epoxide hydrolases are a group of functionally related enzymes that catalyse the cofactor-independent hydrolysis of epoxides to their corresponding vicinal diols by the addition of a water molecule. Here we report the cloning and characterization of an epoxide hydrolase gene from E. lagascae. The structure of the gene is unusual since it lacks introns. A detailed investigation of the transcription pattern of the epoxide hydrolase gene shows that the gene is induced during germination. We have used in situ hybridization to identify in which tissues the gene is expressed during germination. We speculate that this epoxide hydrolase enzyme is involved in the catabolism of epoxidated fatty acids during germination of E. lagascae seeds.


1994 ◽  
Vol 42 (6) ◽  
pp. 827-831 ◽  
Author(s):  
O Hermanson ◽  
H Ericson ◽  
G Sanchez-Watts ◽  
A G Watts ◽  
A Blomqvist

We describe a protocol for simultaneous light microscopic visualization of a neuron's efferent projections and its expression of mRNA. We have combined immunohistochemical visualization of the retrograde marker cholera toxin subunit B (CTb) with autoradiographic visualization of 35S-labeled cRNA probes. Injections of CTb were made into rat brain. Immunoreactivity for CTb was demonstrated by modification of the peroxidase-anti-peroxidase immunohistochemical technique, with DAB and nickel ammonium sulfate or cobalt acetate as chromogen. On the same sections, in situ hybridization was performed with a 35S-labeled RNA probe complementary to preproenkephalin mRNA or tyrosine hydroxylase mRNA. Many double-labeled neurons were detected. These neurons contained peroxidase reaction product and were covered by an accumulation of silver grains in the overlaying emulsion layer. The present method has several advantages over double-labeling methods using the combination of fluorescent tracers and oligonucleotide probes. Both reaction products are permanent and can be visualized simultaneously by light microscopy. Furthermore, both CTb and cRNA probes are very sensitive markers. In addition, the sections can be counterstained.


2018 ◽  
Author(s):  
Kazuhide Asakawa ◽  
Koichi Kawakami

SummaryCranial motor nuclei in the brainstem innervate diverse types of head and neck muscles. Failure in establishing these neuromuscular connections causes congenital cranial dysinnervation disorders (CCDDs) characterized by abnormal craniofacial movements. However, mechanisms that link cranial motor nuclei to target muscles are poorly understood at the molecular level. Here, we report that protocadherin-mediated repulsion mediates neuromuscular connection in the ocular motor system in zebrafish. We identify pools of abducens motor neurons that are topographically arranged according to soma size and convergently innervate a single muscle. Disruptions of Duane retraction syndrome-associated transcription factors reveal that these neurons require Mafba/MAFB, but not Sall4/SALL4, for differentiation. Furthermore, genetic perturbations of Pcdh17/Protocadherin-17 result in defective axon growth and soma clumping, thereby abolishing neuromuscular connectivity. Our results suggest that protocadherin-mediated repulsion forms the central topography and efferent projection pattern of the abducens nucleus following Mafba-dependent specification, and imply potential involvement of protocadherins in CCDD etiology.


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