The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival.
Deeann Wallis,Melanie J. Hamblen,Yi Zhou,Koen J. T. Venken,Armin Schumacher,H. Leighton Grimes,Huda Y. Zoghbi,Stuart H. Orkin,Hugo J. Bellen +8 more
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Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death.Abstract:
Gfi1 was first identified as causing interleukin 2-independent growth in T cells and lymphomagenesis in mice. Much work has shown that Gfi1 and Gfi1b, a second mouse homolog, play pivotal roles in blood cell lineage differentiation. However, neither Gfi1 nor Gfi1b has been implicated in nervous system development, even though their invertebrate homologues, senseless in Drosophila and pag-3 in C. elegans are expressed and required in the nervous system. We show that Gfi1 mRNA is expressed in many areas that give rise to neuronal cells during embryonic development in mouse, and that Gfi1 protein has a more restricted expression pattern. By E12.5 Gfi1 mRNA is expressed in both the CNS and PNS as well as in many sensory epithelia including the developing inner ear epithelia. At later developmental stages, Gfi1 expression in the ear is refined to the hair cells and neurons throughout the inner ear. Gfi1 protein is expressed in a more restricted pattern in specialized sensory cells of the PNS, including the eye, presumptive Merkel cells, the lung and hair cells of the inner ear. Gfi1 mutant mice display behavioral defects that are consistent with inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. They have a unique inner ear phenotype in that the vestibular and cochlear hair cells are differentially affected. Although Gfi1-deficient mice initially specify inner ear hair cells, these hair cells are disorganized in both the vestibule and cochlea. The outer hair cells of the cochlea are improperly innervated and express neuronal markers that are not normally expressed in these cells. Furthermore, Gfi1 mutant mice lose all cochlear hair cells just prior to and soon after birth through apoptosis. Finally, by five months of age there is also a dramatic reduction in the number of cochlear neurons. Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death.read more
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References
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Comprehensive insect physiology, biochemistry, and pharmacology
G. A. Kerkut,L. I. Gilbert +1 more
Journal ArticleDOI
Math1: an essential gene for the generation of inner ear hair cells.
Nessan A. Bermingham,Bassem A. Hassan,Steven D. Price,Melissa A. Vollrath,Nissim Ben-Arie,Ruth Anne Eatock,Hugo J. Bellen,Anna Lysakowski,Huda Y. Zoghbi +8 more
TL;DR: Math1, a mouse homolog of the Drosophila proneural gene atonal, is expressed in inner ear sensory epithelia, and this gene is thus required for the genesis of hair cells.
Journal ArticleDOI
Requirement of Math1 for Secretory Cell Lineage Commitment in the Mouse Intestine
TL;DR: It is found that loss of Math1 leads to depletion of goblet, enteroendocrine, and Paneth cells without affecting enterocytes, and this suggests that secretory cells (goblet,Enteroendocrin, andPaneth cells) arise from a common progenitor that expresses Math1, whereas absorptive cells (enterocytes) arose from a progenitors that isMath1-independent.
Journal ArticleDOI
Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears.
J L Zheng,Wei-Qiang Gao +1 more
TL;DR: It is reported here that overexpression of Math1, a mouse homolog of the Drosophila gene atonal, in postnatal rat cochlear explant cultures resulted in extra hair cells, and immature postnatal mammalian inner ears retained the competence to generate new hair cells.
Journal ArticleDOI
neurogenin1 Is Essential for the Determination of Neuronal Precursors for Proximal Cranial Sensory Ganglia
TL;DR: These data and those of Fode et al. (1998 [this issue of Neuron]) identify ngns as vertebrate neuronal determination genes, analogous to myoD and myf5 in myogenesis.