Mutations giving rise to anatomical defects in the inner ear have been
isolated in a large scale screen for mutations causing visible abnorm
alities in the zebrafish embryo (Haffter, P., Granato, M., Brand, M. e
t al. (1996) Development 123, 1-36). 58 mutants have been classified a
s having a primary ear phenotype; these fall into several phenotypic c
lasses, affecting presence or size of the otoliths, size and shape of
the otic vesicle and formation of the semicircular canals, and define
at least 20 complementation groups. Mutations in seven genes cause los
s of one or both otoliths, but do not appear to affect development of
other structures within the ear. Mutations in seven genes affect morph
ology and patterning of the inner ear epithelium, including formation
of the semicircular canals and, in some, development of sensory patche
s (maculae and cristae). Within this class, dog-eared mutants show abn
ormal development of semicircular canals and lack cristae within the e
ar, while in van gogh, semicircular canals fail to form altogether, re
sulting in a tiny otic vesicle containing a single sensory patch. Both
these mutants show defects in the expression of homeobox genes within
the otic vesicle. In a further class of mutants, ear size is affected
while patterning appears to be relatively normal; mutations in three
genes cause expansion of the otic vesicle, while in little ears and mi
crotic, the ear is abnormally small, but still contains all five senso
ry patches, as in the wild type. Many of the ear and otolith mutants s
how an expected behavioural phenotype: embryos fail to balance correct
ly, and may swim on their sides, upside down, or in circles. Several m
utants with similar balance defects have also been isolated that have
no obvious structural ear defect, but that may include mutants with ve
stibular dysfunction of the inner ear (Granato, M., van Eeden, F. J. M
., Schach, U. et al. (1996) Development, 123, 399-413,). Mutations in
19 genes causing primary defects in other structures also show an ear
defect. In particular, ear phenotypes are often found in conjunction w
ith defects of neural crest derivatives (pigment cells and/or cartilag
inous elements of the jaw). At least one mutant, dog-eared, shows defe
cts in both the ear and another placodally derived sensory system, the
lateral line, while hypersensitive mutants have additional trunk late
ral line organs.