Elliott KL , Houston DW , Fritzsch B .

P30 DC010362 NIDCD NIH HHS , R01 GM083999 NIGMS NIH HHS , R01 DC055095590 NIDCD NIH HHS

	Figure 1: Stage 46 Xenopus laevis ‘three-eared’ frogs. Stage 46 Xenopus laevis ‘three-eared’ frogs. (a) Embryo with a transplanted third ear in the native orientation. (b) Embryo with a transplanted ear rotated 90 degrees from the native ear. (a’) Higher magnification of the natively-oriented transplanted ear and the right native ear in A. (b’) Higher magnification of the 90 degree rotated transplanted ear and the right native ear in B. (c) Three-dimensional reconstruction of a 90 degree rotated transplanted ear next to the native ear. Endolymphatic space is magenta, endolymphatic duct is cyan, and the hair cells are green. Native, unmanipulated ears are labeled ‘Ear’ and are circled with a black dotted line. Transplanted ears are indicated with a white arrow and are circled with a white dotted line. U, utricle; S, saccule. Blue and yellow arrows indicate ear orientation. Scale bar is 0.5†mm.
	Figure 2: Swimming behavior of normal (two-eared), ‘three-eared’ and ‘one-eared’ frogs. Swimming behavior of normal (two-eared), ‘three-eared’ and ‘one-eared’ frogs. (a–d) Examples of embroys analyzed for their swimming behavior: (a) control, (b) normally-positioned third ear, (c) rotated third ear, and (d) one-eared. (a’–d’) Quantification of percent time spent in various swimming orientations in the first ten seconds of recorded observation for each group of animals: (a’) control (n = 7), (b’)normally-positioned third ear (n = 12), (c’) rotated third ear (n = 11), (d’) one eared (n = 6). Behaviors other than upright swimming (blue) were pooled and referred to as “other behaviors” (orange). All comparisons are significant at p < 0.05 except where noted with horizontal bars and NS, not significant. Error bars reflect the standard error of the means. (e–h) Examples of swimming behaviors observed: (e) upright swimming, (f) upside down, (g) swimming on side, (h) spinning.
	Figure 3: Inner ear afferent projections. Inner ear afferent projections. (a) Animal in which inner ear afferents projected entirely together in the VIIIth ganglion. (b) Animal in which inner ear afferents from the natively-oriented transplanted ear projected in their own ‘VIIIth’ ganglion and entered the hindbrain separate from the inner ear afferents from the native VIIIth ganglion. (c) Animal in which the inner ear afferents from the 90 degrees rotated transplanted ear entered the hindbrain from both in its own ‘VIIIth’ ganglion and with the native VIIIth ganglion. (d) Animal in which the inner ear afferents leave the natively-oriented transplanted ear both in its own ‘VIIIth’ ganglion and along with the native VIIIth ganglion. Green arrowheads indicate projections from the transplanted ear. Red arrowheads indicate projections from the native ear. V, trigeminal nerve. Scale bar is 100†µm.
	Figure 4: Overlap and segregation of inner ear afferents from transplanted and native ears. Overlap and segregation of inner ear afferents from transplanted and native ears. (a-a’) Hindbrain from two animals in which the transplanted ear was in the native orientation showing overlap of sensory neurons from the native (red) and transplanted (green) ears. (b-b’) Hindbrain from two animals in which the transplanted ear was rotated by 90 degrees with respect to the native ear showing segregation of sensory neurons from the native (red) and transplanted (green) ears. Insets indicate the transplanted ear orientation. Red and green arrows indicate lipophilic dye placement. (a”) Intensity histogram from an animal with the transplanted ear (green) in line with the native ear (red) shows an overlap of intensity profiles in a single optical section. (b”) Intensity histogram from an animal with the transplanted ear (green) rotated by 90 degrees with respect to the native ear (red) shows a segregation of intensity profiles in a single optical section. (c) Hindbrain showing the native projection when only the control ear was on one side (red). (d) Mean percent overlap and standard error of sensory neurons from the native and transplanted ears for animals in which the transplanted ear was in line with or rotated by 90 degrees with respect to the native ear. 5 animals were analyzed for each condition. Each animal is the mean of measurements taken from 3 different optical sections. Error bars reflect the standard error of the means. ***, p<0.001. Scale bar is 25†µm.
	Figure 1. Stage 46 Xenopus laevis ‘three-eared’ frogs.(a) Embryo with a transplanted third ear in the native orientation. (b) Embryo with a transplanted ear rotated 90 degrees from the native ear. (a’) Higher magnification of the natively-oriented transplanted ear and the right native ear in A. (b’) Higher magnification of the 90 degree rotated transplanted ear and the right native ear in B. (c) Three-dimensional reconstruction of a 90 degree rotated transplanted ear next to the native ear. Endolymphatic space is magenta, endolymphatic duct is cyan, and the hair cells are green. Native, unmanipulated ears are labeled ‘Ear’ and are circled with a black dotted line. Transplanted ears are indicated with a white arrow and are circled with a white dotted line. U, utricle; S, saccule. Blue and yellow arrows indicate ear orientation. Scale bar is 0.5†mm.
	Figure 2. Swimming behavior of normal (two-eared), ‘three-eared’ and ‘one-eared’ frogs.(a–d) Examples of embroys analyzed for their swimming behavior: (a) control, (b) normally-positioned third ear, (c) rotated third ear, and (d) one-eared. (a’–d’) Quantification of percent time spent in various swimming orientations in the first ten seconds of recorded observation for each group of animals: (a’) control (n = 7), (b’)normally-positioned third ear (n = 12), (c’) rotated third ear (n = 11), (d’) one eared (n = 6). Behaviors other than upright swimming (blue) were pooled and referred to as “other behaviors” (orange). All comparisons are significant at p < 0.05 except where noted with horizontal bars and NS, not significant. Error bars reflect the standard error of the means. (e–h) Examples of swimming behaviors observed: (e) upright swimming, (f) upside down, (g) swimming on side, (h) spinning.
	Figure 3. Inner ear afferent projections.(a) Animal in which inner ear afferents projected entirely together in the VIIIth ganglion. (b) Animal in which inner ear afferents from the natively-oriented transplanted ear projected in their own ‘VIIIth’ ganglion and entered the hindbrain separate from the inner ear afferents from the native VIIIth ganglion. (c) Animal in which the inner ear afferents from the 90 degrees rotated transplanted ear entered the hindbrain from both in its own ‘VIIIth’ ganglion and with the native VIIIth ganglion. (d) Animal in which the inner ear afferents leave the natively-oriented transplanted ear both in its own ‘VIIIth’ ganglion and along with the native VIIIth ganglion. Green arrowheads indicate projections from the transplanted ear. Red arrowheads indicate projections from the native ear. V, trigeminal nerve. Scale bar is 100†µm.
	Figure 4. Overlap and segregation of inner ear afferents from transplanted and native ears.(a-a’) Hindbrain from two animals in which the transplanted ear was in the native orientation showing overlap of sensory neurons from the native (red) and transplanted (green) ears. (b-b’) Hindbrain from two animals in which the transplanted ear was rotated by 90 degrees with respect to the native ear showing segregation of sensory neurons from the native (red) and transplanted (green) ears. Insets indicate the transplanted ear orientation. Red and green arrows indicate lipophilic dye placement. (a”) Intensity histogram from an animal with the transplanted ear (green) in line with the native ear (red) shows an overlap of intensity profiles in a single optical section. (b”) Intensity histogram from an animal with the transplanted ear (green) rotated by 90 degrees with respect to the native ear (red) shows a segregation of intensity profiles in a single optical section. (c) Hindbrain showing the native projection when only the control ear was on one side (red). (d) Mean percent overlap and standard error of sensory neurons from the native and transplanted ears for animals in which the transplanted ear was in line with or rotated by 90 degrees with respect to the native ear. 5 animals were analyzed for each condition. Each animal is the mean of measurements taken from 3 different optical sections. Error bars reflect the standard error of the means. ***, p<0.001. Scale bar is 25†µm.

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