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Updated: Jul 19, 2025
Neural Tube Closure in Mouse Whole Embryo Culture
Published on: October 21, 2011
The loop-tail mouse model displays open and closed caudal neural tube defects
Beatriz Fernández-Santos1, Marta Reyes-Corral1, José Manuel Caro-Vega1
1Institute of Biomedicine of Seville (IBiS)/Virgen del Rocío University Hospital/CSIC/University of Seville, 41013 Seville, Spain.
Abstract:
Neural tube defects (NTDs) are the second most common cause of congenital malformations and are often studied in animal models. Loop-tail (Lp) mice carry a mutation in the Vangl2 gene, a member of the Wnt-planar cell polarity pathway. In Vangl2+/Lp embryos, the mutation induces a failure in the completion of caudal neural tube closure, but only a small percentage of embryos develop open spina bifida. Here, we show that the majority of Vangl2+/Lp embryos developed caudal closed NTDs and presented cellular aggregates that may facilitate the sealing of these defects. The cellular aggregates expressed neural crest cell markers and, using these as a readout, we describe a systematic method to assess the severity of the neural tube dorsal fusion failure. We observed that this defect worsened in combination with other NTD mutants, Daam1 and Grhl3. Besides, we found that in Vangl2+/Lp embryos, these NTDs were resistant to maternal folic acid and inositol supplementation. Loop-tail mice provide a useful model for research on the molecular interactions involved in the development of open and closed NTDs and for the design of prevention strategies for these diseases.
Insights
Loop-tail mice with a Vangl2 mutation show a high incidence of closed neural tube defects (NTDs). Cellular aggregates aid defect sealing, but these NTDs resist folic acid and inositol supplementation.
Area of Science:
- Developmental biology
- Genetics
- Teratology
Background:
- Neural tube defects (NTDs) are common congenital malformations.
- Loop-tail (Lp) mice possess a mutation in Vangl2, crucial for the Wnt-planar cell polarity pathway.
Purpose of the Study:
- Investigate caudal neural tube closure in Vangl2+/Lp mouse embryos.
- Characterize cellular aggregates and their role in NTD sealing.
- Assess the impact of genetic background and supplementation on NTDs.
Main Methods:
- Analysis of Vangl2+/Lp mouse embryos.
- Histological examination and assessment of cellular aggregates.
- Evaluation of NTD severity in combination with other mutants (Daam1, Grhl3).
- Testing the efficacy of maternal folic acid and inositol supplementation.
Main Results:
- Vangl2+/Lp embryos predominantly exhibit closed caudal NTDs.
- Cellular aggregates expressing neural crest markers are observed and may facilitate defect closure.
- NTD severity increases when combined with Daam1 or Grhl3 mutations.
- These NTDs are unresponsive to maternal folic acid and inositol supplementation.
Conclusions:
- Vangl2+/Lp mice offer a valuable model for studying both open and closed NTDs.
- Cellular aggregates play a role in neural tube closure.
- Current supplementation strategies may not be effective for these specific NTDs.
