Early innervation and differentiation of hair cells in the vestibular epithelia of mouse embryos: SEM and TEM study

Abstract

Early afferent innervation and differentiation of sensory vestibular cells were studied in mouse embryos from gestation day (GD) 13 to 16. Afferent neurites were found as early as GD 13 in the epithelium when there were no clearly differentiated sensory cells. By GD 14 the earliest sensory cells which exhibited short hair bundles at their luminal pole were then contacted by afferent endings at their basal part. On GD 15 nerve endings establishing specialized synaptic contacts, characterized by asymmetrical membrane densities and synaptic bodies, were observed. At this stage, microtubules contacting the presynaptic membranes, as well as coated vesicles were found. On GD 16 the hair cells were multi-afferented and numerous synaptic bodies were found. These results showing a concomitance between the hair cell differentiation and the establishment of nerve contacts are discussed with particular respect to nerve-hair cell interactions during sensory differentiation. This study does not point to a primary induction of vestibular hair cell differentiation by nerve endings, but it is consistent with the possibility that the ingrowth of nerve fibers is one of many factors that influence the differentiation of receptor cells. With respect to synapse formation, it is assumed that the location of synaptic bodies at presynaptic densities is determined by the arrival of afferent nerve endings.

Orbital spaceflight during pregnancy shapes function of mammalian vestibular system.

“…Numbers of changes in each vector are expressed in degrees (angle) per second (time) as coded from inflight videorecordings. (Altman & Bayer, 1980) G11.5-15.5 Differentiation of neurons within vestibular nuclei 9.5 (Theiler, 1989;Sher, 1971) 11.5 (Altman & Bayer, 1982) G12 Formation of otocyst 10-12 (Ruben, 1967) 12-14 (Altman & Bayer, 1982) G13.5-14.5 Formation of vestibular (otic) ganglion cells 10.5 (Sher, 1971;Tello, 1931) 13 (Ashwell & Zhang, 1998) G13.5 Afferent processes of vestibular ganglion cells invade the macula utricle and saccule and cristae of the semicircular canals 11-12 (Fritzsch & Nichols, 1993) 13-14 a G13.5-14.5 Efferent nerve endings first approach hair cells 13-17 (Ruben, 1967) 15-19 (Altman & Bayer, 1980) G15.5-19.5 Peak hair cell mitosis in crista ampullaris, maculae of saccules, and utricles 15 (Mbiene, Favre, & Sans, 1988) 17 a G17.5 Afferent synaptogenesis with hair cells begins 18-P10 (Rusch, Lysakowski, & Eatock, 1998) 20-P12 a G20.5-P12 Morphological differentiation into Type I and Type II hair cells P28 (Rusch, Lysakowski, & Eatock, 1998) P30 a P30 Fully mature morphological and physiological innervation…”

Developmental Acquisition of Voltage-Dependent Conductances and Sensory Signaling in Hair Cells of the Embryonic Mouse Inner Ear

“…Several possible functions come to mind. Innervation of embryonic vestibular epithelia begins as early as E15, and functional synaptogenesis of bouton afferents with type II cells might follow shortly thereafter (Mbiene et al, 1988). Because vestibular hair cells become mechanosensitive at E17 (Géléoc and Holt, 2003), we predict that the developmental shift in resting potential to more hyperpolarized values will yield larger transduction currents and, in turn, larger receptor potentials.…”

“…Concurrently, the kinocilium grows and is eccentrically placed establishing hair bundle polarity and orientation. Bouton synaptic contacts between hair cells and afferent nerve fibers form as early as E15 (Mbiene et al, 1988), which is presumably followed by functional synaptogenesis. Calyceal afferent endings and morphological differentiation into flask-shaped type I cells begin to take shape several days before birth.…”

Development of the Vestibular System

“…This arrangement is characteristic of what has been described as the initial stage of formation of the hair tuft in the mouse [12]. Most of the sensory epithelium in mouse vestibular organs is composed of a pseudo-stratification of undifferentiated cells at E14 [12,13]. From embryonic day 14 (E14) to postnatal day 2 (P2), terminal mitoses of hair cells and supporting cells occur, with a peak at E16 [14].…”

“…In the embryonic stage, the maturation gradient of hair cells as described by terminal mitoses [22], ciliogenesis [5] and synaptogenesis [13] is also consistent with the developmental appearance of neuron-specific enolase and calbindin-D28K (protein markers that respectively indicate differentiation and synaptic activity of neurons) in the vestibular epithelium of the mouse [23] and human [24]. In the mouse [25], these changes parallel the morphological sequence of maturation from apex to base in the cristae and centre to periphery in the maculae [24,26].…”