# Dysregulated RNA metabolism in cell fate of maternal diabetes-induced neural tube defects > **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $668,211 ## Abstract ABSTRACT Pregestational diabetes induces neural tube defects (NTDs), the second most common birth defects. We and others have shown that cellular stress, altered cell fate and epigenetic and non-coding RNA alterations are critically involved in diabetic embryopathy. How neuroepithelial cell fate is altered by non-coding RNAs in diabetic pregnancy is obscure. We showed that restoring miR-322 expression suppressed by maternal diabetes ameliorated neuroepithelial cell apoptosis and NTDs, revealed that the RNA binding protein RBM47 was a miR- 322 target, and found that exosomes from vascular Flk1 positive progenitors specifically targeted neuroepithelial cells during neurulation. Exosomal delivery of the RBM47-expressing DNA vector to embryos resulted in NTDs. RBM47 binds to the long non-coding RNA (lncRNA), NEAT1, to stabilize it. Exosome-mediated delivery of NEAT1 to embryos induces NTDs. Thus, we hypothesize that maternal diabetes dysregulates RNA metabolism by repressing miR-322, upregulating RBM47 and stabilizing NEAT1 in the neuroepithelium. Restoring miR- 322 or deleting either Rbm47 or Neat1 attenuates neuroepithelial cell apoptosis, senescence, neurogenesis impairment and NTD formation. miR-322 deletion or overexpressing either Rbm47 or Neat1 mimics diabetes to alter cell fate and induce NTDs. To test our hypothesis, we proposed three specific aims. Aim 1 will determine whether miR-322 is essential for neurulation and its reduction contributes to maternal diabetes-induced neuroepithelial cell dysfunction and NTD formation. We hypothesize that maternal diabetes-repressed miR-322 causes senescence and inhibits neurogenesis by altering gene expression in spatial and cell-type specific manners in the neuroepithelium. Aim 2 will investigate whether increased RBM47 mediates the teratogenicity of diabetes by affecting neuroepithelial cell fates leading to NTD formation. Our hypothesis is that miR-322 targets RBM47 for degradation and maternal diabetes increases RBM47 expression by repressing miR-322, and that RBM47 conditional deletion in the neuroepithelium ameliorates neuroepithelial cell fate alteration and NTD formation in diabetic pregnancy. Aim 3 will determine whether increased NEAT1 mediates the teratogenic effect of maternal diabetes by altering neuroepithelial cell function and ultimately promoting NTD formation. We hypothesize that maternal diabetes increases NEAT1 via RBM47-mediated stabilization and that NEAT1 deficiency reverses neuroepithelial cell fate alterations and blocks NTDs in diabetic embryopathy. Alteration in miRNA, RNA binding protein, and lncRNA alterations are involved in human NTDs. Revealing this mechanism in linking miRNA to lncRNA via RBM47 is a novel epigenetic regulation in diabetic embryopathy. ## Key facts - **NIH application ID:** 11050038 - **Project number:** 1R01HD114794-01A1 - **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE - **Principal Investigator:** Wei-Bin Shen - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $668,211 - **Award type:** 1 - **Project period:** 2024-09-17 → 2029-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11050038 ## Citation > US National Institutes of Health, RePORTER application 11050038, Dysregulated RNA metabolism in cell fate of maternal diabetes-induced neural tube defects (1R01HD114794-01A1). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/11050038. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*