Tzy-Wen Gong

• University of Michigan

The ability to detect sound is a genetic trait essential for survival and subject to evolutionary selection. With industrial operations and the use of power tools and equipment, noise impinges on many aspects of our daily life and we are subject to frequent bouts of excessive noise. Although exposure to less intense noise can lead to temporary loss...

Diverse cellular and environmental stresses can activate the heat shock response, an evolutionarily conserved mechanism to protect proteins from denaturation. Stressors activate heat shock transcription factor 1 (HSF1), which binds to heat shock elements in the genes for heat shock proteins, leading to rapid induction of these important molecular c...

Failure of the primary lip and palate to fuse leads to clefts of the lip, a birth defect with an incidence of 1 for every 500 in some races. Epithelial cells lining the facial processes of the primary lip and palate, the lateral and medial nasal processes (LNP and MNP), must first make contact to go through a series of highly regulated and coordina...

Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndro...

The mammalian vestibular epithelium has a limited capacity for spontaneous hair cell regeneration. The mechanism underlying the regeneration is not well understood. Because the Notch signaling pathway mediates the formation of the sensory epithelial mosaic patterning during ear development, it may also play a role in hair cell regeneration in the m...

The absence of thyroid hormone (TH) during late gestation and early infancy can cause irreparable deafness in both humans and rodents. A variety of rodent models have been used in an effort to identify the underlying molecular mechanism. Here, we characterize a mouse model of secondary hypothyroidism, pituitary transcription factor 1 (Pit1(dw)), wh...

: A report on the Sixth Molecular Biology of Hearing and Deafness Conference, Hinxton, UK, 11-14 July 2007.

The vertebrate cochlea is a complex organ optimized for sound transduction. Auditory hair cells, with their precisely arranged stereocilia bundles, transduce sound waves to electrical signals that are transmitted to the brain. Mutations in the unconventional myosin XV cause deafness in both human DFNB3 families and in shaker 2 (sh2) mice as a resul...

In epithelial sheets, clearance of dead cells may occur by one of several routes, including extrusion into the lumen, phagocytic clearance by invading lymphocytes, or phagocytosis by neighboring cells. The fate of dead cochlear outer hair cells is unclear. We investigated the fate of the "corpses" of dead outer hair cells in guinea pigs and mice fo...

The molecular mechanisms by which the primordia of the midface grow and fuse to form the primary palate are not well characterized. This is in spite of the fact that failure of growth and/or fusion of these facial primordia leads to the common human craniofacial birth defects, clefts of the lip with or without clefts of the palate. Members of the t...

In mammals, exposure to intense noise produces a permanent hearing loss called permanent threshold shift (PTS), whereas a moderate noise produces only a temporary threshold shift (TTS). Little is known about the molecular responses to such high intensity noise exposures. In this study we used gene arrays to examine the early response to acoustic ov...

The Kresge Hearing Research Institute-3 (KHRI-3) antibody binds to a guinea pig inner ear supporting cell antigen (IESCA) and causes hearing loss. To gain insight into the mechanism of antibody-induced hearing loss, we used antibody immunoaffinity purification to isolate the IESCA, which was then sequenced by mass spectroscopy, revealing 10 guinea...

E3 ubiquitin ligases target proteins for degradation by adding ubiquitin residues. We characterized full-length cDNAs for human and mouse UBE3B, a novel HECT-domain E3 ligase, and analyzed the structure of human UBE3B on chromosome 12q24.1. Alternative splicing of exon 20 of UBE3B generated two major transcripts. The 5.7-kb mRNA lacked exon 20 and...

On Dec 15, 2003 this sequence version replaced gi:29469992.

High-throughput DNA microarray technology allows for the assessment of large numbers of genes and can reveal gene expression in a specific region, differential gene expression between regions, as well as changes in gene expression under changing experimental conditions or with a particular disease. The present study used a gene array to profile nor...

Mammalian MACF1 (Macrophin1; previously named ACF7) is a giant cytoskeletal linker protein with three known isoforms that arise by alternative splicing. We isolated a 19.1-kb cDNA encoding a fourth isoform (MACF1-4) with a unique N-terminus. Instead of an N-terminal actin-binding domain found in the other three isoforms, MACF1-4 has eight plectin r...

Glial cell line-derived neurotrophic factor (GDNF) is a survival factor for many neuronal cell types which signals through a heterodimer receptor consisting of GDNF-family receptor α 1 (GFRα-1) and Ret (arranged during ransformation). GDNF expression has previously been reported in the inner hair cells of the rat cochlea, with expression of GFRα-1...

Acoustic overstimulation has very different outcomes in birds and mammals. When noise exposure kills hair cells in birds, these cells can regenerate and hearing will recover. In mammals, however, the hair cell loss, and resulting hearing loss, is permanent. Changes in gene expression form the basis for important biological processes, including repa...

Differential gene expression forms the basis for development, differentiation, regeneration, and plasticity of tissues and organs. We describe two methods to identify differentially expressed genes. Differential display, a PCR-based approach, compares the expression of subsets of genes under two or more conditions. Gene arrays, or DNA microarrays,...

The chickWDR1gene is expressed at higher levels in the chick basilar papilla after acoustic overstimulation. The 3.3-kbWDR1cDNA encodes a novel 67-kDa protein containing nine WD40 repeats, motifs that mediate protein–protein interactions. The predicted WDR1 protein has high sequence identity to WD40-repeat proteins in budding yeast (Saccharomyces c...

Two full length avian cDNAs for ornithine decarboxylase antizyme were isolated from a chicken cochlear cDNA library and differed in length through use of alternative poly(A) addition signals. The chick antizyme protein sequence predicted by translational frameshifting of the mRNA is 216 amino acids long and is more similar to Xenopus antizyme than...

We used the technique of differential display of RNA to identify genes expressed in the chick auditory epithelium in response to acoustic trauma. In the course of these studies, we identified a partial cDNA (amplicon) derived from the 3 untranslated region of cRZF, a chicken gene encoding a zinc finger protein with a Cys3HisCys4 (RING) motif that c...

Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/42144/1/335-9-2-171_9n2p171.pdf

Two full length avian cDNAs for ornithine decarboxylase antizyme were isolated from a chicken cochlear cDNA library and differed in length through use of alternative poly(A) addition signals. The chick antizyme protein sequence predicted by translational frameshifting of the mRNA is 216 amino acids long and is more similar to Xenopus antizyme than...

Differential display of mRNA is a technique that enables the researcher to compare genes expressed in two or more different tissues or in the same tissue or cell under different conditions. The method is based on polymerase chain reaction amplification and comparison of specific subsets of mRNA. We have used this method to clone partial complementa...

CDC42 is a member of the ras superfamily of small GTP-binding proteins that are related through the highly conserved GTP-binding domain and are involved in signal transduction pathways. Two full-length CDC42 cDNAs have been isolated: a 2148-bp chick cochlea cDNA and a 2063-bp mouse liver cDNA. Each encodes a CDC42 protein of 191 amino acids. The av...

We isolated a full-length cDNA encoding a novel 278 amino acid β subunit of Na,K-ATPase from a mouse retinal cDNA library. The highest sequence identity was to known β3 isoforms, identifying the protein as the mouse β3 subunit of Na,K-ATPase. Two transcripts, 1.75 kb and 2.1 kb, probably arise from use of alternative poly(A) addition signals.

CDC42 is a member of the ras superfamily of small GTP-binding proteins that are related through the highly conserved GTP-binding domain and are involved in signal transduction pathways. Two full-length CDC42 cDNAs have been isolated: a 2148-bp chick cochlea cDNA and a 2063-bp mouse liver cDNA. Each encodes a CDC42 protein of 191 amino acids. The av...

We used differential display of mRNA, a method based on reverse transcriptase-PCR, to identify genes whose expression increases in response to acoustic trauma in the chick basilar papilla. Identifying these genes would provide insight into processes involved in repair of the damaged epithelium or in hair cell regeneration. We compared mRNA from the...