Establishing the tonotopic organization of the mammalian cochlea

Jinwoong Bok 한국실험동물학회 2018 한국실험동물학회 학술발표대회 논문집 Vol.2018 No.7

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear.

Bok, Jinwoong,Raft, Steven,Kong, Kyoung-Ah,Koo, Soo Kyung,Drä,ger, Ursula C,Wu, Doris K National Academy of Sciences 2011 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.108 No.1

<P>Vertebrate hearing and balance are based in complex asymmetries of inner ear structure. Here, we identify retinoic acid (RA) as an extrinsic signal that acts directly on the ear rudiment to affect its compartmentalization along the anterior-posterior axis. A rostrocaudal wave of RA activity, generated by tissues surrounding the nascent ear, induces distinct responses from anterior and posterior halves of the inner ear rudiment. Prolonged response to RA by posterior otic tissue correlates with Tbx1 transcription and formation of mostly nonsensory inner ear structures. By contrast, anterior otic tissue displays only a brief response to RA and forms neuronal elements and most sensory structures of the inner ear.</P>

Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells

Bok, Jinwoong,Zenczak, Colleen,Hwang, Chan Ho,Wu, Doris K. National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.34

<P>Neural precursor cells of the central nervous system undergo successive temporal waves of terminal division, each of which is soon followed by the onset of cell differentiation. The organ of Corti in the mammalian cochlea develops differently, such that precursors at the apex are the first to exit from the cell cycle but the last to begin differentiating as mechanosensory hair cells. Using a tissue-specific knockout approach in mice, we show that this unique temporal pattern of sensory cell development requires that the adjacent auditory (spiral) ganglion serve as a source of the signaling molecule Sonic hedgehog (Shh). In the absence of this signaling, the cochlear duct is shortened, sensory hair cell precursors exit from the cell cycle prematurely, and hair cell differentiation closely follows cell cycle exit in a similar apical-to-basal direction. The dynamic relationship between the restriction of <I>Shh</I> expression in the developing spiral ganglion and its proximity to regions of the growing cochlear duct dictates the timing of terminal mitosis of hair cell precursors and their subsequent differentiation.</P>

Roles of stereociliary links in the outer hair cells in hearing

Jinwoong Bok 한국실험동물학회 2020 한국실험동물학회 학술발표대회 논문집 Vol.2020 No.2

고속도로 교량의 저탄소 건설기술 적용 방안

최진웅,강상규,김유복,Choi, Jinwoong,Kang, Sang-Gyu,Kim, Yoo-Bok 한국건설순환자원학회 2022 한국건설순환자원학회지 Vol.17 No.2

Grp78 is a Novel Downstream Target Gene of Hoxc8 Homeoprotein

Jin Joo Kang,Jinwoong Bok,Myoung Hee Kim 대한의생명과학회 2011 Biomedical Science Letters Vol.17 No.1

Previously, we have identified 14 putative downstream target genes of Hoxc8 homeoprotein in F9 murine embryonic teratocarcinoma cells through proteomics analysis. Among those, we tested a possibility of a DNA-k type molecular chaperone, Grp78, as a direct downstream target of Hoxc8, by cloning a 2.4 kb upstream region of murine Grp78 into a reporter plasmid and by testing if Hoxc8 can regulate its expression. We observed that Hoxc8 proteins could transactivate the reporter gene, which was affected by small interference RNAs (siRNAs) against to Hoxc8, suggesting that Grp78 is a novel downstream target of Hoxc8 in vivo.

CTCF is required for maintenance of auditory hair cells and hearing function in the mouse cochlea

Ma, Ji-Hyun,Kim, Hyoung-Pyo,Bok, Jinwoong,Shin, Jeong-Oh Elsevier 2018 Biochemical and biophysical research communication Vol.503 No.4

<P><B>Abstract</B></P> <P>Auditory hair cells play an essential role in hearing. These cells convert sound waves, mechanical stimuli, into electrical signals that are conveyed to the brain via spiral ganglion neurons. The hair cells are located in the organ of Corti within the cochlea. They assemble in a special arrangement with three rows of outer hair cells and one row of inner hair cells. The proper differentiation and preservation of auditory hair cells are essential for acquiring and maintaining hearing function, respectively. Many genetic regulatory mechanisms underlying hair-cell differentiation and maintenance have been elucidated to date. However, the role of epigenetic regulation in hair-cell differentiation and maintenance has not been definitively demonstrated. CTCF is an essential epigenetic component that plays a primary role in the organization of global chromatin architecture. To determine the role of CTCF in mammalian hair cells, we specifically deleted <I>Ctcf</I> in developing hair cells by crossing <I>Ctcf</I> <SUP> <I>fl/fl</I> </SUP> mice with <I>Gfi1</I> <SUP> <I>Cre/+</I> </SUP> mice. <I>Gfi1</I> <SUP> <I>Cre</I> </SUP> <I>; Ctcf</I> <SUP> <I>fl/fl</I> </SUP> mice did not exhibit obvious developmental defects in hair cells until postnatal day 8. However, at 3 weeks, the <I>Ctcf</I> deficiency caused intermittent degeneration of the stereociliary bundles of outer hair cells, resulting in profound hearing impairment. At 5 weeks, most hair cells were degenerated in <I>Gfi1</I> <SUP> <I>Cre</I> </SUP> <I>; Ctcf</I> <SUP> <I>fl/fl</I> </SUP> mice, and defects in other structures of the organ of Corti, such as the tunnel of Corti and Nuel's space, became apparent. These results suggest that CTCF plays an essential role in maintaining hair cells and hearing function in mammalian cochlea.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Identification of evidence for autoimmune pathology of bilateral sudden sensorineural hearing loss using proteomic analysis

Lee, Jeon Mi,Kim, Jin Young,Bok, Jinwoong,Kim, Kyu-Sung,Choi, Jae Young,Kim, Sung Huhn Elsevier 2017 Clinical immunology Vol.183 No.-

<P><B>Abstract</B></P> <P>Sudden sensorineural hearing loss (S-SNHL) is an inner ear disorder with an abrupt hearing loss occurring <3days. The pathologic mechanism of the disease remains unclear, although autoimmunity has been regarded as one of the suggested causes, especially in bilateral form. In this study, we aimed to provide evidence for the involvement of autoimmunity in bilateral S-SNHL using proteomic approaches such as ProtoArray®, western blotting, immunoprecipitation, and liquid column mass spectrometry for mass screening of candidate antigens and autoantibodies based on the hypothesis that multiple autoantibodies and target antigens must exist in order for autoimmune bilateral S-SNHL to develop. As the final outcome, we have proven the involvement of autoimmunity in the disease, and investigated the existence of circulating autoantibodies and candidate antigens. These findings could provide basic evidence necessary for the development of diagnostic biomarkers as well as the understanding of the pathological mechanisms underlying bilateral S-SNHL.</P> <P>S-SNHL: sudden sensorineural hearing loss; LC-MS: liquid chromatography-mass spectrometry; MS: mass spectrometry; autoAb: autoantibody; 1-DE: one-dimensional electrophoresis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Evidences for autoimmunity were revealed by proteomic techniques in bilateral S-SNHL. </LI> <LI> Multiple autoantibodies and their target antigens were involved in the autoimmunity. </LI> <LI> The results can provide a basis for understanding autoimmune inner ear disorder. </LI> <LI> Biomarkers in autoimmune inner ear disorder can be developed based on the results. </LI> </UL> </P>

Retinoic Acid Induces Abnormal Palate During Embryogenesis in Rat

Jeong Oh Shin,Hyoung Woo Park,Jinwoong Bok,Myoung Hee Kim 대한의생명과학회 2010 Biomedical Science Letters Vol.16 No.1

In order to understand the effects of all-trans-RA on palate development, RA was injected into the abdominal cavity of pregnant mice and then the embryos were taken in the following days and analyzed morphologically as well as molecular biologically. When RA was administered at the stage of E11 or E15, the overall craniofacial development was retarded. The length from jaw to eye was shortened, compared to that of normal group. When the E11 embryos were exposed to RA, cleft lip was also found along with the cleft palate. In vitro palate culture experiment also revealed that RA caused cleft palate. When RT-PCR was performed, early stage administration of RA at E11 inhibited the upregulation of Hoxa7 expression at E15 through E17. Whereas in control group, high level of Hoxa7 expression was detected in the palate of E15 to E17. In the case of Bax, the expression was decreased from E16, while remaining constant in control group. When TUNEL analysis was performed following the RA treatment at E15, TUNEL positive cells were detected in the mesenchymal cells as well as epithelial cells of palatal shelves of E16 and in E17 embryos. Whereas in normal control, TUNEL positive cells were observed mostly at the epithelium around the nasal cavity and oral cavity where rugae is made. These results altogether indicate that exposure to RA during palate development causes facial deformity including cleft palate and cleft lip by modulating the expression of homeotic genes such as Hoxa7 as well as an apoptosis-related gene, Bax, and thus malregulating the apoptosis.

Inhibition of the Zeb family prevents murine palatogenesis through regulation of apoptosis and the cell cycle

Shin, Jeong-Oh,Lee, Jong-Min,Bok, Jinwoong,Jung, Han-Sung Elsevier 2018 Biochemical and biophysical research communication Vol.506 No.1

<P><B>Abstract</B></P> <P>Mammalian palate separates the oral and nasal cavities for normal feeding, breathing and speech. The palatal shelves are a pair of maxillary prominences that consist of the neural crest-derived mesenchyme and surrounding epithelium. Palatogenesis is completed by the fusion of the midline epithelial seam (MES) after the medial edge epithelium (MEE) cells make contact between the palatal shelves. Various cellular and molecular events, such as apoptosis, cell proliferation, cell migration, and epithelial-mesenchymal transition (EMT), are involved in palatogenesis. The Zeb family of transcription factors is an essential player during normal embryonic development. The distinct role of the Zeb family has not been thoroughly elucidated to date. In mouse palate, the Zeb family factors are expressed in the palatal mesenchyme until MEE contact. Interestingly, the expression of the Zeb family has also been observed in MES, which is already fused with the mesenchymal region. The regulatory roles of the Zeb family in palatogenesis have not been elucidated to date. The purpose of this study is to determine the Zeb family effects on the cellular events. To investigate the functions of the Zeb family, siRNA targeting Zeb family was used to treat <I>in vitro</I> organ culture for temporary inhibition of the Zeb family during palatogenesis. In the cultured palate containing siRNA, MES was clearly observed, and E-cadherin, an epithelial marker, was still expressed. Inhibition of the Zeb family results in the suppression of apoptosis, increased cell proliferation, and defective cell migration in the developing palate. Our data suggest that the Zeb family plays multiple roles in the stimulation and inhibition of apoptosis and cell proliferation and efficient mesenchymal cell migration during palatogenesis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Zeb family is an essential player during proper palate development. </LI> <LI> Zeb family regulate apoptosis during palatal fusion. </LI> <LI> siRNA targeting Zeb family induce E-cadherin in remaining MES. </LI> <LI> Zeb family regulate cell proliferation and mesenchymal cell migration during palatogenesis. </LI> </UL> </P>