Journal article
Lmx1a is required for segregation of sensory epithelia and normal ear histogenesis and morphogenesis
Cell and tissue research, Vol.334(3), pp.339-358
12/2008
DOI: 10.1007/s00441-008-0709-2
PMCID: PMC2654344
PMID: 18985389
Abstract
At E8.5, the LIM-homeodomain factor
Lmx1a
is expressed throughout the otic placode but becomes developmentally restricted to non-sensory epithelia of the ear (endolymphatic duct, ductus reuniens, cochlea lateral wall). We confirm here that the ears of newborn dreher (
Lmx1a
dr
) mutants are dysmorphic. Hair cell markers such as
Atoh1
and Myo7 reveal for the first time that newborn
Lmx1a
mutants have only three sensory epithelia: two enlarged canal cristae and one fused epithelium comprising an amalgamation of the cochlea, saccule and utricle, a “cochlear-gravistatic” endorgan. The enlarged anterior canal crista develops by fusion of horizontal and anterior crista whereas the posterior crista fuses with an enlarged papilla neglecta that may extend into the cochlear lateral wall. In the fused endorgan the cochlear region is distinguished from the vestibular region by markers such as
Gata3
, the presence of a tectorial membrane and cochlea-specific innervation. The cochlea-like apex displays minor disorganization of the hair and supporting cells. This contrasts with the basal half of the cochlear region which shows a vestibular epithelium-like organization of hair cells and supporting cells. The dismorphic features of the cochlea are also reflected in altered gene expression patterns.
Fgf8
expression expands from inner hair cells in the apex to most hair cells in the base. Two supporting cell marker proteins,
Sox2
and Prox1, also differ in their cellular distribution between the base and the apex.
Sox2
expression expands in mutant canal cristae prior to their enlargement and fusion and displays a more diffuse and widespread expression in the base of the cochlear region whereas Prox1 is not detected in the base. These changes in
Sox2
and Prox1 expression suggest that
Lmx1a
expression restricts and sharpens
Sox2
expression thereby defining non-sensory and sensory epithelium. The adult
Lmx1a
mutant organ of Corti showed a loss of cochlear hair cells, suggesting that long term hair cell maintenance is also disrupted in these mutants.
Details
- Title: Subtitle
- Lmx1a is required for segregation of sensory epithelia and normal ear histogenesis and morphogenesis
- Creators
- David H Nichols - Department of Biomedical Sciences, Creighton University, Omaha, NebraskaSarah Pauley - Department of Biomedical Sciences, Creighton University, Omaha, NebraskaIsrat Jahan - Department of Biology, University of Iowa, Iowa City, IowaKirk W Beisel - Department of Biomedical Sciences, Creighton University, Omaha, NebraskaKathleen J Millen - Departments of Human Genetics and Neurology, University of Chicago, Chicago, IllinoisBernd Fritzsch - Department of Biology, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Cell and tissue research, Vol.334(3), pp.339-358
- DOI
- 10.1007/s00441-008-0709-2
- PMID
- 18985389
- PMCID
- PMC2654344
- NLM abbreviation
- Cell Tissue Res
- ISSN
- 0302-766X
- eISSN
- 1432-0878
- Language
- English
- Date published
- 12/2008
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070741602771
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