Evidence for reopening of the cranial neural tube in mouse embryos treated with cadmium chloride

Diabetes-induced early embryonic death is accompanied by an increased expression of tumour necrosis factor alpha (TNF-alpha) in the embryonic microenvironment. The aim of the present study was to evaluate whether diabetes-induced embryopathic stress may also alter the expression of TNF-alpha produced by the embryo itself. As a model, whole postimplantation embryos were cultured for 24 h in a medium with high concentrations of glucose, one of the main diabetes-associated teratogenic metabolites. An anomaly such as an open neural tube was used as an end-point characterizing the glucose-induced teratogenic effect and the number of somites was counted to evaluate growth retardation induced by glucose. The expression of TNF-alpha (by immunohistochemistry), apoptosis (by TdT-mediated dUTP nick-end labelling; TUNEL) and the activity of caspases 3 and 8 (by a fluorometric assay) were evaluated in normal and malformed embryos. Ninety-seven per cent of the embryos exposed to 1300 mg glucose dl(-1) exhibited an open neural tube. The percentage of malformed embryos was smaller in media containing 800 and 500 mg glucose dl(-1) (68 and 37%, respectively) but it still exceeded significantly the value registered in embryos developing in a normoglycaemic medium (12%). In addition, a significant decrease in the number of somites was observed in embryos developing in media containing 1300 and 800 mg glucose dl(-1). Malformed embryos exhibited a greater number of nuclei that were positive in the TUNEL assay as well as a higher amount of active caspase 8 compared with normal embryos (with closed neural folds). TNF-alpha expression was detected in the neuroepithelial layer of the neural tube of the malformed embryos, whereas the expression of this cytokine was weak, if detectable, in normal embryos. Together, these findings indicate that TNF-alpha produced by the embryo may be involved in regulating the response of embryos to diabetes-generated embryopathic stress.

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RNA-Seq analysis reveals candidate genes that may explain neural tube defects in mouse embryos lacking SR-BI

Placenta ◽

10.1016/j.placenta.2017.01.071 ◽

2017 ◽

Vol 51 ◽

pp. 118-119

Author(s):

N. Santander ◽

C. Lizama ◽

A. Quiroz ◽

A. Rigotti ◽

D. Busso

Keyword(s):

Candidate Genes ◽

Neural Tube ◽

Neural Tube Defects ◽

Mouse Embryos ◽

Rna Seq

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Neural tube development in mutant (curly tail) and normal mouse embryos: the timing of posterior neuropore closure in vivo and in vitro

Development ◽

10.1242/dev.69.1.151 ◽

1982 ◽

Vol 69 (1) ◽

pp. 151-167

Author(s):

A. J. Copp ◽

M. J. Seller ◽

P. E. Polani

Keyword(s):

Neural Tube ◽

Neural Tube Defects ◽

Mouse Embryos ◽

Injection Technique ◽

Posterior Neuropore ◽

Curly Tail ◽

Mechanisms Of Development ◽

Delayed Closure

A dye-injection technique has been used to determine the developmental stage at which posterior neuropore (PNP) closure occurs in normal and mutant curly tail mouse embryos. In vivo, the majority of non-mutant embryos undergo PNP closure between 30 and 34 somites whereas approximately 50% of all mutant embryos show delayed closure, and around 20% maintain an open PNP even at advanced stages of development. A similar result has been found for embryos developing in vitro from the headfold stage. Later in development, 50–60% of mutant embryos in vivo develop tail flexion defects, and 15–20% lumbosacral myeloschisis. This supports the view that delayed PNP closure is the main developmental lesion leading to the appearance of caudal neural tube defects in curly tail mice. The neural tube is closed in the region of tail flexion defects, but it is locally overexpanded and abnormal in position. The significance of these observations is discussed in relation to possible mechanisms of development of lumbosacral and caudal neural tube defects. This paper constitutes the first demonstration of the development of a genetically induced malformation in vitro.

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Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia

Journal of Developmental Biology ◽

10.3390/jdb7010005 ◽

2019 ◽

Vol 7 (1) ◽

pp. 5 ◽

Cited By ~ 3

Author(s):

Yuan Wang ◽

Huiqing Zeng ◽

Aimin Liu

Keyword(s):

Neural Tube ◽

Protein Level ◽

Primary Cilia ◽

Cultured Cells ◽

Mouse Embryos ◽

Proteolytic Processing ◽

Partial Activation ◽

Maximal Activation ◽

Ectopic Activation ◽

Hh Signaling

The primary cilia play essential roles in Hh-dependent Gli2 activation and Gli3 proteolytic processing in mammals. However, the roles of the cilia in Gli1 activation remain unresolved due to the loss of Gli1 transcription in cilia mutant embryos, and the inability to address this question by overexpression in cultured cells. Here, we address the roles of the cilia in Gli1 activation by expressing Gli1 from the Gli2 locus in mouse embryos. We find that the maximal activation of Gli1 depends on the cilia, but partial activation of Gli1 by Smo-mediated Hh signaling exists in the absence of the cilia. Combined with reduced Gli3 repressors, this partial activation of Gli1 leads to dorsal expansion of V3 interneuron and motor neuron domains in the absence of the cilia. Moreover, expressing Gli1 from the Gli2 locus in the presence of reduced Sufu has no recognizable impact on neural tube patterning, suggesting an imbalance between the dosages of Gli and Sufu does not explain the extra Gli1 activity. Finally, a non-ciliary Gli2 variant present at a higher level than Gli1 when expressed from the Gli2 locus fails to activate Hh pathway ectopically in the absence of the cilia, suggesting that increased protein level is unlikely the major factor underlying the ectopic activation of Hh signaling by Gli1 in the absence of the cilia.

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