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. Author manuscript; available in PMC: 2017 Jan 15.
Published in final edited form as: Dev Biol. 2015 Nov 7;409(2):329–342. doi: 10.1016/j.ydbio.2015.09.024

Figure 6.

Figure 6

Development of cranial nerves that are critical for feeding and swallowing is disrupted in LgDel mice. A. A comparison of cranial nerve differentiation at E10.5 in WT and LgDel mice. Left: a dorsal view of the hindbrain from an E10.5 WT (left) and E10.5 LgDel embryo (right) in which the cranial nerves have been labeled in the whole specimen using a neurofilament antibody. The arrows indicate the diminished distance between gCN V and gCN VII in the LgDel. The asterisks indicate the diminished presence of presumed motor axons exiting into CN V and CN VII in the LgDel. Finally, gCN IX and X are distinct entities in the WT, but are fused and appear to be shifted anteriorly (possibly due to diminished size of the anterior regions), in the LgDel. Right: High magnification lateral views compare WT cranial nerves with those compromised in the LgDel mouse. Both CN V and CN VII appear smaller and dysmorphic. The most consistent changes (statistically significant based on blind scoring by 4 independent observers; [9]) are: diminished thickness and lack of branching of all three divisions of CN V (ophthalmic-op; maxillary-mx; mandibular-md; arrows and bracket; upper panels); lack of terminal bifurcated branching in CN VII (arrows, middle panels), and fusions or anomalous axon branches that join CN IX and X (arrows, lower panels). B. Distinct changes in cranial nerve development are seen in Tbx1+/− E10.5 embryos. Left: The distance between CN V and VII, seen in a dorsal view of the neurofilament labeled E10.5 hindbrain in the Tbx1+/− embryo is not diminished (arrows), as is the case in the LgDel (shown for comparison in the right panel), and the size and branching of CN V and VII are comparable to WT. In contrast, we found fusions and anomalous axon fascicles between CN IX and X, and these approximate the phenotypes seen in the LgDel embryo. We note, however, that CN IX and X appear smaller in the LgDel than in the Tbx1+/− mouse. Right: WT CN IX and X (top) are separated (arrows) and their axons extend in an orderly fashion both centrally and peripherally. Tbx1+/− CN IX and X are fused (arrows), as in the LgDel (compare with lower right panel in A). These fusions in the Tbx1+/− embryo happen at the same frequency as those seen in the LgDel [9], supporting a key role for heterozygous loss of function of Tbx1+/− for this CN phenotype.