Dynamic imaging and quantitative analysis of cranial neural tube closure in the mouse embryo using optical coherence tomography

Abstract

Abstract:Neural tube closure is a critical feature of central nervous system morphogenesis during embryonic development. Failure of this process leads to neural tube defects, one of the most common forms of human congenital defects. Although molecular and genetic studies in model organisms have provided insights into the genes and proteins that are required for normal neural tube development, complications associated with live imaging of neural tube closure in mammals limit efficient morphological analyses. Here, we report the use of optical coherence tomography (OCT) for dynamic imaging and quantitative assessment of cranial neural tube closure in live mouse embryos in culture. Through time-lapse imaging, we captured two neural tube closure mechanisms in different cranial regions, zipper-like closure of the hindbrain region and button-like closure of the midbrain region. We also used OCT imaging for phenotypic characterization of a neural tube defect in a mouse mutant. These results suggest that the described approach is a useful tool for live dynamic analysis of normal neural tube closure and neural tube defects in the mouse model. 131-137 (1991). 7. G. Morriss-Kay, H. Wood, and W. H. Chen, "Normal neurulation in mammals," Ciba Foundation symposium 181, 51-63 (1994). 8. L. R. Campbell, D. H. Dayton, and G. S. Sohal, "Neural tube defects: A review of human and animal studies on the etiology of neural tube defects," Teratology 34(2), 171-187 (1986). 9. Y. Yamaguchi and M. Miura, "How to form and close the brain: insight into the mechanism of cranial neural tube closure in mammals," Cell. Mol. Life Sci. 70(17), 3171-3186 (2013). 10. D. M. Juriloff and M. J. Harris, "Mouse models for neural tube closure defects," Hum. Mol. Genet. 9(6), 993-1000 (2000).

Evaluating the effects of maternal alcohol consumption on murine fetal brain vasculature using optical coherence tomography

“…For example, OCT is capable of imaging blood vessels less than 50 μm in diameter, which other modalities such as ultrasound biomicroscopy are incapable of resolving . We have demonstrated the superior capabilities of OCT for mouse and rat embryonic imaging during normal and abnormal development .…”

Evaluating biomechanical properties of murine embryos using Brillouin microscopy and optical coherence tomography

“…By imaging different regions of the neural tube at different developmental stages of the murine embryo, we hope to study how changes in mechanical properties of cells influence NTDs. Since OCT has already been used for imaging and analyzing the closure of a live murine embryonic neural tube, 58 our future work will entail imaging this process with Br-OCT and understanding the influence of teratogens and other environmental factors on neural tube closure.…”

Single‐site neural tube closure in human embryos revisited

“…Only two studies concerned sections of mouse embryos (Sadler, ; Greene and Copp, ; Pyrgaki et al, ), but the presented figures remain inconclusive to show multiple sites of fusion within one embryo since the successive sections are lacking or the neural walls lie closely together but show no fusion. Also, the stunning dynamic images of neural tube closure in mouse embryos of Pyrgaki and Wang did not display this kind of fusion (Pyrgaki et al, ; Wang et al, ). The electron microscope images published by Juriloff et al (), however, showed a degree of fusion that is significant enough to consider that neural tube closure in mouse embryos occurs at multiple sites.…”