QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 16 December 2004
doi: 10.1242/dev.01587

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.01587v1 132/2/371    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mackereth, M. D. Articles by Riley, B. B. Search for Related Content PubMed PubMed Citation Articles by Mackereth, M. D. Articles by Riley, B. B. Social Bookmarking                         What's this?

Zebrafish pax8 is required for otic placode induction and plays a redundant role with Pax2 genes in the maintenance of the otic placode

Melinda D. Mackereth^1,*, Su-Jin Kwak^2,*, Andreas Fritz¹ and Bruce B. Riley^2,

¹ Department of Biology, Emory University, Atlanta, GA 30322, USA
² Biology Department, Texas A&M University, College Station, TX 77843-3258, USA

Author for correspondence (e-mail: briley{at}mail.bio.tamu.edu)

Accepted 17 November 2004

Vertebrate Pax2 and Pax8 proteins are closely related transcription factors hypothesized to regulate early aspects of inner ear development. In zebrafish and mouse, Pax8 expression is the earliest known marker of otic induction, and Pax2 homologs are expressed at slightly later stages of placodal development. Analysis of compound mutants has not been reported. To facilitate analysis of zebrafish pax8, we completed sequencing of the entire gene, including the 5' and 3' UTRs. pax8 transcripts undergo complex alternative splicing to generate at least ten distinct isoforms. Two different subclasses of pax8 splice isoforms encode different translation initiation sites. Antisense morpholinos (MOs) were designed to block translation from both start sites, and four additional MOs were designed to target different exon-intron boundaries to block splicing. Injection of MOs, individually and in various combinations, generated similar phenotypes. Otic induction was impaired, and otic vesicles were small. Regional ear markers were expressed correctly, but hair cell production was significantly reduced. This phenotype was strongly enhanced by simultaneously disrupting either of the co-inducers fgf3 or fgf8, or another early regulator, dlx3b, which is thought to act in a parallel pathway. In contrast, the phenotype caused by disrupting foxi1, which is required for pax8 expression, was not enhanced by simultaneously disrupting pax8. Disrupting pax8, pax2a and pax2b did not further impair otic induction relative to loss of pax8 alone. However, the amount of otic tissue gradually decreased in pax8-pax2a-pax2b-deficient embryos such that no otic tissue was detectable by 24 hours post-fertilization. Loss of otic tissue did not correlate with increased cell death, suggesting that otic cells dedifferentiate or redifferentiate as other cell type(s). These data show that pax8 is initially required for normal otic induction, and subsequently pax8, pax2a and pax2b act redundantly to maintain otic fate.

Key words: Preplacodal domain, Otic placode, Genetic network, Paired, Fibroblast growth factor, forkhead, distal-less, msxC

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Cruz, J.-C. Shiao, B.-K. Liao, C.-J. Huang, and P.-P. Hwang Plasma membrane calcium ATPase required for semicircular canal formation and otolith growth in the zebrafish inner ear J. Exp. Biol., March 1, 2009; 212(5): 639 - 647. [Abstract] [Full Text] [PDF]

				K. Dutton, L. Abbas, J. Spencer, C. Brannon, C. Mowbray, M. Nikaido, R. N. Kelsh, and T. T. Whitfield A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle Dis. Model. Mech., January 1, 2009; 2(1-2): 68 - 83. [Abstract] [Full Text] [PDF]

				C. S. Jayasena, T. Ohyama, N. Segil, and A. K. Groves Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode Development, July 1, 2008; 135(13): 2251 - 2261. [Abstract] [Full Text] [PDF]

				T. Wendl, D. Adzic, J. J. Schoenebeck, S. Scholpp, M. Brand, D. Yelon, and K. B. Rohr Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals Development, August 1, 2007; 134(15): 2871 - 2879. [Abstract] [Full Text] [PDF]

				S. Hans and M. Westerfield Changes in retinoic acid signaling alter otic patterning Development, July 1, 2007; 134(13): 2449 - 2458. [Abstract] [Full Text] [PDF]

				A. Nechiporuk, T. Linbo, K. D. Poss, and D. W. Raible Specification of epibranchial placodes in zebrafish Development, February 1, 2007; 134(3): 611 - 623. [Abstract] [Full Text] [PDF]

				B. B. Millimaki, E. M. Sweet, M. S. Dhason, and B. B. Riley Zebrafish atoh1 genes: classic proneural activity in the inner ear and regulation by Fgf and Notch Development, January 15, 2007; 134(2): 295 - 305. [Abstract] [Full Text] [PDF]

				J. C. Clarke, S. R. Patel, R. M. Raymond Jr, S. Andrew, B. G. Robinson, G. R. Dressler, and P. D. Brophy Regulation of c-Ret in the developing kidney is responsive to Pax2 gene dosage Hum. Mol. Genet., December 1, 2006; 15(23): 3420 - 3428. [Abstract] [Full Text] [PDF]

				O. Bricaud and A. Collazo The Transcription Factor six1 Inhibits Neuronal and Promotes Hair Cell Fate in the Developing Zebrafish (Danio rerio) Inner Ear J. Neurosci., October 11, 2006; 26(41): 10438 - 10451. [Abstract] [Full Text] [PDF]