Altered gene expression with abnormal patterning of the telencephalon in embryos of diabetic Albino Swiss mice

Liao, Dongmei; Ng, Yen Kaow; Tay, Samuel Sam Wah; Ling, Eng‐Ang; Dheen, S. Thameem

doi:10.1007/s00125-004-1351-5

Cited by 28 publications

(35 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that maternal diabetes induces neural tube defects by altering the expression of various genes involved in the early neural tube patterning that occurs concomitantly with neural induction from NSCs [2,5,6,25]. The proliferation and differentiation of NSCs can be influenced by various maternal factors such as growth factors, cytokines and teratogens, leading to alteration of the cell-fate choice that determines the size, shape and histogenesis of the neural tube [10,15,25].…”

Section: Discussionmentioning

confidence: 99%

“…Although the molecular mechanisms by which maternal diabetes induces NTDs are not known with certainty, it has been suggested that altered expression of genes involved in neural tube development may contribute to the NTD [2,5,6]. Since the neural tube is derived from neural stem cells (NSCs), which are self-renewing, multipotent progenitors, giving rise to different cell types that compose the nervous system, such as neurons, astrocytes and oligodendrocytes, it is possible that maternal diabetes may influence the proliferation and differentiation of NSCs leading to neural tube defects during embryogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…A recent study reported that Shh promotes the development of neurons and oligodendrocytes from forebrain NSCs by activating the expression of Ascl1 and Olig2, with a modulation of BMP signalling [20]. Previously, it has been demonstrated that altered expression of Shh and Bmp4 and their downstream genes is associated with the abnormal patterning of the telencephalon in embryos of diabetic mice [5]. Hence it is hypothesised that maternal diabetes alters the expression of some developmental control genes leading to abnormal proliferation and cell-fate choice of NSCs, thereby resulting in patterning defects during neural tube development.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells

Tay

Ling

et al. 2006

Diabetologia

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis: Maternal diabetes induces neural tube defects during embryogenesis. Since the neural tube is derived from neural stem cells (NSCs), it is hypothesised that in diabetic pregnancy neural tube defects result from altered expression of developmental control genes, leading to abnormal proliferation and cell-fate choice of NSCs. Materials and methods: Cell viability, proliferation index and apoptosis of NSCs and differentiated cells from mice exposed to physiological or high glucose concentration medium were examined by a tetrazolium salt assay, 5-bromo-2′-deoxyuridine incorporation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and immunocytochemistry. Expression of developmental genes, including sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4), neurogenin 1/2 (Neurog1/2), achaete-scute complex-like 1 (Ascl1), oligodendrocyte transcription factor 1 (Olig1), oligodendrocyte lineage transcription factor 2 (Olig2), hairy and enhancer of split 1/5 (Hes1/5) and delta-like 1 (Dll1), was analysed by real-time RT-PCR. Proliferation index and neuronal specification in the forebrain of embryos at embryonic day 11.5 were examined histologically. Results: High glucose decreased the proliferation of NSCs and differentiated cells. The incidence of apoptosis was increased in NSCs treated with high glucose, but not in the differentiated cells. High glucose also accelerated neuronal and glial differentiation from NSCs. The decreased proliferation index and early differentiation of neurons were evident in the telencephalon of embryos derived from diabetic mice. Exposure to high glucose altered the mRNA expression levels of Shh, Bmp4, Neurog1/2, Ascl1, Hes1, Dll1 and Olig1 in NSCs and Shh, Dll1, Neurog1/2 and Hes5 in differentiated cells. Conclusions/interpretation: The changes in proliferation and differentiation of NSCs exposed to high glucose are associated with altered expression of genes that are involved in cell-cycle progression and cell-fate specification during neurulation. These changes may form the basis for the defective neural tube patterning observed in embryos of diabetic pregnancies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells

Tay

Ling

et al. 2006

Diabetologia

Self Cite

View full text Add to dashboard Cite

show abstract

“…Sonic hedgehog (Shh) and Bmp exert ventralizing and dorsalizing patterning influences respectively. Diabetes reduces Bmp expression and upregulates Shh expression in mice resulting in thicker ventral regions of the forebrain and a syntelencephaly-like presentation (Liao et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

Hrubec

Prater

Toops

et al. 2005

Birth Defects Research Pt B

View full text Add to dashboard Cite

BACKGROUND: Maternal diabetes can induce a number of developmental abnormalities in laboratory animals and humans, including facial deformities and defects in neural tube closure. The incidence of birth defects in newborns of diabetic women is approximately 3–5 times higher than among non‐diabetics. In mice, non‐specific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including diabetes induced neural tube defects. This study was conducted to determine whether non‐specific maternal immune stimulation could reduce diabetes‐induced craniofacial defects as well. METHODS: Maternal immune function was stimulated before streptozocin (STZ) treatment by maternal footpad injection with Freund's complete adjuvant (FCA), maternal intraperitoneal (i.p.) injection with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), or maternal i.p. injection with interferon‐γ (IFNγ). Streptozocin (200 mg/kg i.p.) was used to induce hyperglycemia (26–35 mmol blood glucose) in female ICR mice before breeding. Fetuses from 12–18 litters per treatment group, were collected at Day 17 of gestation. RESULTS: Craniofacial defects were observed in fetuses from all hyperglycemic groups. The incidence of defects was significantly decreased in fetuses from dams immune stimulated with IFNγ or GM‐CSF. The most common defects were reduced maxillary and mandibular lengths. Both were prevented by maternal stimulation with GM‐CSF. CONCLUSION: Maternal immune stimulation reduced the incidence of diabetic craniofacial embryopathy. The mechanisms for these protective effects are unknown but may involve maternal or fetal production of cytokines or growth factors that protect the fetus from the dysregulatory effects of hyperglycemia. Birth Defects Res Part B 2006. © 2005 Wiley‐Liss, Inc.

show abstract

“…We have reported maternal diabetes-induced malformations in several parts of the brain including the forebrain (telencephalon), spinal neural tube, choroid plexus (CP) and ventricles in mouse embryos [19,20] . The impaired development of CP by maternal diabetes results in decreased production of cerebro-spinal fluid which is proposed to cause defective patterning and shaping of the brain during development in diabetic pregnancy [21][22][23][24] .…”

Section: Characterisation Of Ntdsmentioning

confidence: 99%

Frontiers in research on maternal diabetes-induced neural tube defects: Past, present and future

Sudhaharan

Bay²,

Tay³

et al. 2012

WJD

View full text Add to dashboard Cite

Diabetes mellitus rightly regarded as a silent-epidemic is continually on the rise and estimated to have a global prevalence of 6.4 % as of 2010. Diabetes during pregnancy is a well known risk factor for congenital anomalies in various organ systems that contribute to neonatal mortality, including cardiovascular, gastrointestinal, genitourinary and neurological systems, among which the neural tube defects are frequently reported. Over the last two to three decades, several groups around the world have focussed on identifying the molecular cues and cellular changes resulting in altered gene expression and the morphological defects and in diabetic pregnancy. In recent years, the focus has gradually shifted to looking at pre-programmed changes and activation of epigenetic mechanisms that cause altered gene expression. While several theories such as oxidative stress, hypoxia, and apoptosis triggered due to hyperglycemic conditions have been proposed and proven for being the cause for these defects, the exact mechanism or the link between how high glucose can alter gene expression/transcriptome and activate epigenetic mechanisms is largely unknown. Although preconceptual control of diabetes, (i.e., managing glucose levels during pregnancy), and in utero therapies has been proposed as an effective solution for managing diabetes during pregnancy, the impact that a fluctuating glycemic index can have on foetal development has not been evaluated in detail. A tight glycemic control started before pregnancy has shown to reduce the incidence of congenital abnormalities in diabetic mothers. On the other hand, a tight glycemic control after organogenesis and embryogenesis have begun may prove insufficient to prevent or reverse the onset of congenital defects. The importance of determining the extent to which glycemic levels in diabetic mothers should be regulated is critical as foetal hypoglycemia has also been shown to be teratogenic. Finally, the major question remaining is if this whole issue is negligible and not worthy of investigation as the efficient management of diabetes during pregnancy is well in place in many countries.

show abstract

Altered gene expression with abnormal patterning of the telencephalon in embryos of diabetic Albino Swiss mice

Cited by 28 publications

References 53 publications

High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells

High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells

Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

Frontiers in research on maternal diabetes-induced neural tube defects: Past, present and future

Contact Info

Product

Resources

About