The positional cues for formation of individual inner ear components are dependent on pre-established axial information conferred by inductive signals from tissues surrounding the developing inner ear. This review summarizes some of the known molecular pathways involved in establishing the three axes of the inner ear, anterior-posterior (AP), dorsal-ventral (DV) and medial-lateral (ML). Signals required to establish the AP axis of the inner ear are not known, but they do not appear to be derived from the hindbrain. In contrast, the hindbrain is essential for establishing the DV axis of the inner ear by providing inductive signals such as Wnts and Sonic hedgehog. Signaling from the hindbrain is also required for the formation of the ML axis, whereas formation of the lateral wall of the otocyst may be a result of first establishing both the AP and DV axes. In addition, this review addresses how genes induced within the otic epithelium as a result of axial specification continue to mediate inner ear morphogenesis.
KEY WORDS: inner ear, morphogenesis, vertebrate, axial specification, patterningThe vertebrate inner ear is a highly intricate organ (Figure 1). One of the earliest events during inner ear formation is the acquisition of its axial identity from surrounding tissues. In amniotes, this process most likely begins after otic placode formation and involves early cell fate decisions. These early decisions can be classified into three categories: neural, sensory and non-sensory. Neural-fated cells delaminate from the otic epithelium to form neurons of the cochleovestibular ganglion (CVG). Sensory-fated cells eventually develop into sensory hair cells and supporting cells that form various sensory patches within elaborate nonsensory structures. Sensory and non-sensory fated cells most likely interact with each other to coordinate the morphogenetic process. Identifying the inductive signals that confer axial identity and the cascades of molecular and cellular events that follow are essential for elucidating inner ear morphogenesis.
Axial specification of the inner earThe locations where otic placodes develop along the body axis are thought to be dependent on Fibroblast growth factors (Fgfs) emanating from the mesoderm, endoderm and hindbrain (Noramly and Grainger, 2002, Ladher et al., 2005). Details of the otic placode inductive process will be covered by other reviews in this issue. Analyses of mouse hindbrain mutants such as kreisler, Hoxa1 and Fgf3 suggest that the lack of Fgf signaling in the hindbrain alone does not affect placode formation but rather affects subsequent morphogenetic events (Kiernan et al., 2002). There is some indication that inner ear malformations in these hindbrain mutants may be due to defects in axial patterning (Choo Int. J. Dev. Biol. 51: 521-533 (2007) al., 2006). In chicken, otic axial specification occurs after placode formation, whereas this process appears to occur much earlier in salamanders (Harrison, 1936, Bok et al., 2005. The timing of axial specification in mi...