PMID- 9334402 OWN - NLM STAT- MEDLINE DCOM- 19971120 LR - 20231012 IS - 0270-6474 (Print) IS - 1529-2401 (Electronic) IS - 0270-6474 (Linking) VI - 17 IP - 21 DP - 1997 Nov 1 TI - Analysis of rat vestibular hair cell development and regeneration using calretinin as an early marker. PG - 8270-82 AB - Despite increased interest in inner ear hair cell regeneration, it is still unclear what exact mechanisms underlie hair cell regeneration in mammals because of our limited understanding of hair cell development and the lack of specific hair cell markers. In this report, we studied hair cell development using immunohistochemistry on sections prepared from embryonic day (E) 13 to postnatal day 7 rat inner ear tissues. Of many epithelial, neuronal, and glial markers, we found that calcium-binding protein antibodies recognizing calretinin, calmodulin, or parvalbumin labeled immature hair cells in rat vestibular end organs. In particular, calretinin antiserum labeled the initial differentiating hair cells at E15, a stage immediately after the terminal mitosis of hair cell progenitors. The selective immunoreactivity of postmitotic presumptive hair cells, but not supporting cells or peripheral epithelial cells, was confirmed in utricular epithelial sheet cultures. Double labeling with calretinin and bromodeoxyuridine antibodies in long-term cultures showed that only a few mitotic utricular supporting cells became calretinin positive. Thus, although proliferation-mediated regeneration of new hair cells might directly contribute to hair cell regeneration in rat utricles after injury, it is very limited. In addition, double labeling with calretinin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) revealed that differentiated hair cells underwent apoptosis during normal development at late embryonic and early postnatal stages in vivo and in vitro. Therefore, these experiments lay the groundwork for the time course of differentiation, regeneration, and apoptosis of mammalian vestibular hair cells. This work also suggests that calcium-binding proteins are useful markers for studies on inner ear hair cell differentiation and regeneration. FAU - Zheng, J L AU - Zheng JL AD - Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA. FAU - Gao, W Q AU - Gao WQ LA - eng PT - Journal Article PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Biomarkers) RN - 0 (Calb2 protein, rat) RN - 0 (Calbindin 2) RN - 0 (Calmodulin) RN - 0 (Nerve Tissue Proteins) RN - 0 (Parvalbumins) RN - 0 (S100 Calcium Binding Protein G) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Animals MH - Apoptosis MH - Biomarkers MH - Bromodeoxyuridine/analysis MH - Calbindin 2 MH - Calmodulin/analysis MH - Cell Differentiation MH - Cell Division MH - Cells, Cultured MH - Gene Expression Regulation, Developmental MH - Hair Cells, Vestibular/chemistry/*cytology MH - Nerve Regeneration MH - Nerve Tissue Proteins/*analysis MH - Parvalbumins/analysis MH - Rats MH - Rats, Wistar MH - S100 Calcium Binding Protein G/*analysis/genetics MH - Saccule and Utricle/cytology MH - Vestibule, Labyrinth/cytology/embryology/*growth & development/physiology PMC - PMC6573764 EDAT- 1997/10/23 00:00 MHDA- 1997/10/23 00:01 PMCR- 1998/05/01 CRDT- 1997/10/23 00:00 PHST- 1997/10/23 00:00 [pubmed] PHST- 1997/10/23 00:01 [medline] PHST- 1997/10/23 00:00 [entrez] PHST- 1998/05/01 00:00 [pmc-release] AID - 10.1523/JNEUROSCI.17-21-08270.1997 [doi] PST - ppublish SO - J Neurosci. 1997 Nov 1;17(21):8270-82. doi: 10.1523/JNEUROSCI.17-21-08270.1997.