Source: http://aoot.osa.org/boe/abstract.cfm?uri=boe-8-1-407
Timestamp: 2019-04-23 06:56:32+00:00

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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.
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» Visualization 1: MOV (6689 KB) Time-lapse 3D OCT imaging of the cranial neural tube closure in the mouse embryo for over 16 hours.
» Visualization 2: MOV (936 KB) Zipper-like closure of neural tube at the hindbrain region of the mouse embryo.
» Visualization 3: MOV (1638 KB) Button-like closure of neural tube at the midbrain region of the mouse embryo.
Fig. 1 Live mouse embryo culture combined with OCT imaging for analysis of cranial neural tube closure. (A) Setup of the OCT sample arm inside a humidified incubator for static mouse embryo culture (Top); An enlarged side view of the culturing setup for the mouse embryo where a transparent Teflon film is placed on top of the medium to avoid evaporation (Bottom). (B) An example of 3D OCT embryonic imaging with a live mouse embryo at the stage of early E8.0 when the neural plates are formed yet not bent. The green line in the dorsal view indicates the position where the anterior view is taken. Scale bars correspond to 200 µm.
Fig. 2 Time-lapse 3D OCT imaging of the cranial neural tube closure in the mouse embryo for over 16 hours. (A) A 3D image of the mouse embryo shows the three major parts of the cranial region, the forebrain, the midbrain and the hindbrain. (B) 3D images of the mouse embryo at the beginning and ending time points of the imaging session show the size increase and the yolk sac vascular remolding through development. The red arrows indicate the capillary plexus (left) and the remodeled blood vessels (right). (C) Representative frames from 3D OCT time-lapse demonstrate cranial neural tube closure while the embryo is turning (see Visualization 1). In the images of selected time points, the solid, dashed and dotted arrows point at forebrain, midbrain and hindbrain of the embryo, respectively, and the triangle points at a closure initiation site between the forebrain and midbrain. All scale bars correspond to 300 µm. The time stamps of images correspond to Visualization 1. The playback is 5000 times faster.
Fig. 3 Zipper-like closure of neural tube at the hindbrain region of the mouse embryo. (A) Time-resolved 3D OCT images of the mouse embryo hindbrain region show a zipper-like neural tube closure (see Visualization 2). The red arrows point at the site where zipper-like closure occurs. The yellow lines between the head folds (0 min) represent the positions where distances are measured. (B) Distances between neural folds at different line positions plotted over time indicate the zipper-like process of neural tube closure at the hindbrain region. Scale bars correspond to 200 µm. The time stamps of images correspond to Visualization 2. The playback is 5000 times faster.
Fig. 4 Button-like closure of neural tube at the midbrain region of the mouse embryo. (A) Time-resolved 3D OCT images of the mouse embryo midbrain region show a button-like neural tube closure (see Visualization 3). The red arrows point at the sites where button-like closure occurs. The yellow lines between the head folds (0 min) represent the positions where distances are measured. (B) Distances between neural folds at different line positions plotted over time indicate the button-like process of neural tube closure at the midbrain region. Scale bars correspond to 200 µm. The time stamps of images correspond to Visualization 3. The playback is 5000 times faster.
Fig. 5 Phenotypic characterization of neural tube closure at the forebrain of the Wdr19 mutant mouse embryo. 3D OCT images of the forebrain region from the (A) control and (B) Wdr19 mouse embryos at E8.5 show a clear difference in the neural tube phenotype. The red arrows point at the forebrain region. The green lines in the ventral views indicate the locations where the anterior views are taken. The yellow lines in the anterior views show the positions of distance measurement. All scale bars correspond to 300 µm. (C) Quantification for the distance between neural folds at the forebrain region of the embryos show a larger distance (statistically significant) from the Wdr19 embryos in comparison with the control. The central thick lines represent the mean and the whiskers represent the standard deviation. The number of samples N = 10 for both groups. The p value is from a two-sample t test.

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