Related Experiment Video
Updated: Sep 23, 2026
Separation of Mouse Embryonic Facial Ectoderm and Mesenchyme
Published on: April 12, 2013
Neural and orofacial defects in Folp1 knockout mice [corrected]
Louisa S Tang1, Richard H Finnell
1Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030-3303, USA.
Background:
Folic acid is essential for the development of the nervous system and other associated structures. Mice deficient in the folic acid-binding protein one (Folbp1) gene display multiple developmental abnormalities, including neural and craniofacial defects. To better understand potential interactions between Folbp1 gene and selected genes involved in neural and craniofacial morphogenesis, we evaluated the expression patterns of a panel of crucial differentiation markers (Pax-3, En-2, Hox-a1, Shh, Bmp-4, Wnt-1, and Pax-1).
Methods:
Folbp1 mice were supplemented with low dosages of folinic add to rescue nullizygotes from dying in utero before gestational day 10. The gene marker analyses were carried out by in situ hybridization.
Results:
In nullizygote embryos with open cranial neural tube defects, the downregulation of Pax-3 and En-2 in the impaired midbrain, along with an observed upregulation of the ventralizing marker Shh in the expanded floor plate, suggested an important regulatory interaction among these three genes. Moreover, the nullizygotes also exhibit craniofacial abnormalities, such as cleft lip and palate. Pax-3 signals in the impaired medial nasal primordia were significantly increased, whereas Pax-1 showed no expression in the undeveloped lateral nasal processes. Although Shh was downregulated, Bmp-4 was strongly expressed in the medial and lateral nasal processes, highlighting the antagonistic activities of these molecules.
Conclusions:
Impairment of Folbp1 gene function adversely impacts the expression of several critical signaling molecules. Mis-expression of these molecules, perhaps mediated by Shh, may potentially contribute to the observed failure of neural tube closure and the development of craniofacial defects in the mutant mice.
Insights
Folic acid-binding protein 1 (Folbp1) gene deficiency causes neural tube and craniofacial defects in mice. This study reveals Folbp1
Area of Science:
- Developmental biology
- Genetics
- Neuroscience
Background:
- Folic acid is vital for nervous system development.
- Folbp1 gene deficiency in mice leads to neural and craniofacial abnormalities.
- Investigating Folbp1 interactions with key developmental genes is crucial.
Purpose of the Study:
- To examine the expression patterns of differentiation markers (Pax-3, En-2, Hox-a1, Shh, Bmp-4, Wnt-1, Pax-1) in Folbp1-deficient mice.
- To understand the regulatory interactions between Folbp1 and genes involved in neural and craniofacial development.
Main Methods:
- Folbp1-deficient mice were rescued with folinic acid to allow in utero survival.
- In situ hybridization was used to analyze gene marker expression patterns.
Main Results:
- Folbp1 deficiency caused downregulation of Pax-3 and En-2, and upregulation of Shh in midbrain defects.
- Craniofacial abnormalities, including cleft lip and palate, were observed.
- Differential expression of Pax-3, Pax-1, Shh, and Bmp-4 suggests complex regulatory roles in facial development.
Conclusions:
- Folbp1 gene impairment disrupts critical signaling molecules.
- Mis-expression of these molecules, potentially involving Shh, contributes to neural tube closure failure and craniofacial defects.
