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.

Abelló, Independent regulation of Sox3 and Lmx1b by FGF and BMP signaling influences the neurogenic and non-neurogenic domains in the chick otic placode. 2010, Pubmed

Abelló, Independent regulation of Sox3 and Lmx1b by FGF and BMP signaling influences the neurogenic and non-neurogenic domains in the chick otic placode. 2010, Pubmed
Adam, Circuit formation and maintenance--perspectives from the mammalian olfactory bulb. 2010, Pubmed
Allen-Sharpley, Coordinated Eph-ephrin signaling guides migration and axon targeting in the avian auditory system. 2012, Pubmed
Allen-Sharpley, Differential roles for EphA and EphB signaling in segregation and patterning of central vestibulocochlear nerve projections. 2013, Pubmed
Bianchi, Comparison of ephrin-A ligand and EphA receptor distribution in the developing inner ear. 1999, Pubmed
Blackiston, Ectopic eyes outside the head in Xenopus tadpoles provide sensory data for light-mediated learning. 2013, Pubmed , Xenbase
Boss, Activity and the formation of ocular dominance patches in dually innervated tectum of goldfish. 1984, Pubmed
Cheetham, Neuroscience. An olfactory critical period. 2014, Pubmed
Clause, The precise temporal pattern of prehearing spontaneous activity is necessary for tonotopic map refinement. 2014, Pubmed
Constantine-Paton, Eye-specific termination bands in tecta of three-eyed frogs. 1978, Pubmed
Cowan, EphB2 guides axons at the midline and is necessary for normal vestibular function. 2000, Pubmed
Defourny, Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells. 2013, Pubmed
Duncan, Continued expression of GATA3 is necessary for cochlear neurosensory development. 2013, Pubmed
Elliott, Transplantation of Xenopus laevis ears reveals the ability to form afferent and efferent connections with the spinal cord. 2010, Pubmed , Xenbase
Elliott, Transplantation of Xenopus laevis tissues to determine the ability of motor neurons to acquire a novel target. 2013, Pubmed , Xenbase
Fritzsch, Evolution and development of the tetrapod auditory system: an organ of Corti-centric perspective. 2013, Pubmed
Fritzsch, Diffusion and imaging properties of three new lipophilic tracers, NeuroVue Maroon, NeuroVue Red and NeuroVue Green and their use for double and triple labeling of neuronal profile. 2005, Pubmed
Fritzsch, The development of the hindbrain afferent projections in the axolotl: evidence for timing as a specific mechanism of afferent fiber sorting. 2005, Pubmed
Fritzsch, Evolution of vertebrate mechanosensory hair cells and inner ears: toward identifying stimuli that select mutation driven altered morphologies. 2014, Pubmed
Fritzsch, Inner ear development: building a spiral ganglion and an organ of Corti out of unspecified ectoderm. 2015, Pubmed , Xenbase
Fritzsch, Experimental reorganization in the alar plate of the clawed toad, Xenopus laevis. I. Quantitative and qualitative effects of embryonic otocyst extirpation. 1990, Pubmed , Xenbase
Fritzsch, A discrete projection of the sacculus and lagena to a distinct brainstem nucleus in a catfish. 1990, Pubmed
Gliem, Bimodal processing of olfactory information in an amphibian nose: odor responses segregate into a medial and a lateral stream. 2013, Pubmed , Xenbase
Graziadei, Regeneration of olfactory axons and synapse formation in the forebrain after bulbectomy in neonatal mice. 1978, Pubmed
Graziadei, Plasticity of connections of the olfactory sensory neuron: regeneration into the forebrain following bulbectomy in the neonatal mouse. 1979, Pubmed
Graziadei, Ectopic glomerular structures in the olfactory bulb of neonatal and adult mice. 1980, Pubmed
Hubel, Binocular interaction in striate cortex of kittens reared with artificial squint. 1965, Pubmed
Hubel, Ferrier lecture. Functional architecture of macaque monkey visual cortex. 1977, Pubmed
Jahan, Neurod1 regulates survival and formation of connections in mouse ear and brain. 2010, Pubmed
Kirkby, A role for correlated spontaneous activity in the assembly of neural circuits. 2013, Pubmed
Leber, Effect of precocious and delayed afferent arrival on synapse localization on the amphibian Mauthner cell. 1991, Pubmed
Magrassi, Interaction of the transplanted olfactory placode with the optic stalk and the diencephalon in Xenopus laevis embryos. 1985, Pubmed , Xenbase
Maklad, The developmental segregation of posterior crista and saccular vestibular fibers in mice: a carbocyanine tracer study using confocal microscopy. 2002, Pubmed
Maklad, Development of vestibular afferent projections into the hindbrain and their central targets. 2003, Pubmed
Maklad, Development and organization of polarity-specific segregation of primary vestibular afferent fibers in mice. 2010, Pubmed
Meyer, Tetrodotoxin blocks the formation of ocular dominance columns in goldfish. 1982, Pubmed
Morrison, An ultrastructural study of glomeruli associated with vomeronasal organs transplanted into the rat CNS. 1996, Pubmed
Reh, Eye-specific segregation requires neural activity in three-eyed Rana pipiens. 1985, Pubmed
Schmidt, Eye-specific segregation of optic afferents in mammals, fish, and frogs: the role of activity. 1985, Pubmed , Xenbase
Shatz, Pioneer neurons and target selection in cerebral cortical development. 1990, Pubmed
Springer, Optic fiber segregation in goldfish with two eyes innervating one tectal lobe. 1981, Pubmed
Straka, Connecting ears to eye muscles: evolution of a 'simple' reflex arc. 2014, Pubmed
Straka, Canal-specific excitation and inhibition of frog second-order vestibular neurons. 1997, Pubmed
Swindale, Absence of ocular dominance patches in dark-reared cats. 1981, Pubmed
Tonniges, Photo- and bio-physical characterization of novel violet and near-infrared lipophilic fluorophores for neuronal tracing. 2010, Pubmed
Triplett, Molecular guidance of retinotopic map development in the midbrain. 2014, Pubmed
Wiesel, The postnatal development of the visual cortex and the influence of environment. 1982, Pubmed