Expression of ZIC genes in the development of the chick inner ear and nervous system

Abstract

ZIC genes, vertebrate homologues of the Drosophila pair-rule gene odd-paired (opa), function in embryonic pattern formation, in the early stages of central nervous system neurogenesis and in cerebellar maturation. Mouse Zic genes are expressed in restricted, and in some cases overlapping, patterns during development, particularly in the central and peripheral nervous systems. We identified chick ZIC2 in a differential display analysis of the auditory system designed to find genes up-regulated after noise trauma. In this study, we examined the expression of chick ZIC1, ZIC2, and ZIC3 by in situ hybridization in normal inner ear development and in the tissues that influence its development, including the hindbrain, the neural crest, and the periotic mesenchyme. Between Hamburger and Hamilton stages 13 and 24, all three ZIC genes were found in the dorsal periotic mesenchyme adjacent to the developing inner ear. ZIC1 mRNA was expressed in the otocyst epithelium between stages 12 and 24, in some sensory tissue, as well as in a striped pattern in the floorplate of the hindbrain that appears to be complementary to that of Chordin, a gene known to regulate ZIC expression in frogs. Chick ZIC genes are also expressed in the neuroectoderm, paraxial mesenchyme, brain, spinal cord, neural crest, and/or the overlying ectoderm as well as the limb buds. In general, ZIC1 and ZIC2 expression patterns overlapped, although ZIC2 expression was less robust; ZIC3 expression was minimal. These observations suggest that ZIC genes, in addition to their known roles in brain development, may play an important role in the development of the chick inner ear. Developmental Dynamics 226:702-712, 2003.

Bone marrow mesenchymal stem cells are progenitors in vitro for inner ear hair cells

“…This is consistent with the analysis of the Pax2 null mouse (Burton et al, 2004), which appears to develop hair cells despite severe disruption of the normal morphology of the cochlea. The lack of Zic1 expression relative to Zic2 is also found during development of a hair cell phenotype as compared to sensory neurons in the otocyst (Warner et al, 2003) and is thus consistent with the development of a hair cell phenotype. The identification of inductive molecules on chick otocyst cells that are not present in conditioned media will provide further insights into hair cell differentiation.…”

Emerging roles for zic genes in early development

“…2T) Gaston-Massuet et al, 2005). The zic genes of Xenopus, zebrafish, and chicken are also expressed in the somites (Rohr et al, 1999;Warner et al, 2003;Toyama et al, 2004;Fujimi et al, 2006) with a few exceptions Toyama et al, 2004;Fujimi et al, 2006). In particular, the zic5 gene is not expressed in the somites of Xenopus (Fig.…”

Molecular characterization of conditionally immortalized cell lines derived from mouse early embryonic inner ear

“…The last three genes mediate Notch signaling in presumptive SCs in early cochlear patterning (Weir et al, 2000). Zic genes have been postulated to affect the fate of precursor cells common to neurons or sensory HCs by affecting expression of downstream atonal class genes, which may themselves be regulated by bone morphogenetic proteins (BMPs) and their antagonists (Warner et al, 2003;Barald and Kelley, 2004).…”

“…We have studied expression of genes associated with BMP4 and Notch signaling, including BMP4 and related growth factors, BMP receptors, three BMP antagonists (noggin, chordin, and DAN), Notch-1, and its ligand jagged-2. We have also examined the expression of Zic genes, which we hypothesize are downstream effectors of BMP4/chordin antagonistic cascades and potentially important for neuronal or HC specification (Warner et al, 2003;Barald and Kelley, 2004). One of the cell lines, IMO-2B1, which we hypothesize is a good model for an early "precursor cell," has been characterized in detail in this study by real-time quantitative polymerase chain reaction (PCR) with a panel of 50 primer pairs characteristic of HCs, SCs, SNs, and presumptive precursor cells.…”

“…Expression of the zinc-finger-of-thecerebellum gene family members Zic1 and Zic2 (Warner et al, 2003) were measured during the screening of the seven clonal IMO cell lines (Table 1). Many cell lines expressed one or both Zic genes.…”