Time frame of mitral cell development in the mice olfactory bulb

Abstract

Along with tufted cells, mitral cells are the principal projection neurons in the olfactory bulb (OB). During the development of the OB, mitral cells migrate from the ventricular zone to the intermediate zone, where they begin to send axons along the lateral olfactory tract (LOT) to the cortical olfactory zones. Subsequently, they lose their tangential orientation, enabling them to make contact with the axons of the olfactory sensory neurons (OSN) that innervate the whole OB. Here, we investigated the distinct morphological features displayed by developing mitral cells and analyzed the relationship between the changes undertaken by these neurons and the arrival of the OSN axons. Immunostaining for specific markers of developing axons and dendrites, coupled with the use of fluorescent tracers, revealed the morphological changes, the continuous reorientation, and the final refinement that these cells undergo. We found that some of these changes are dependent on the arrival of the OSN axons. Indeed, we identified three main chronological events: 1) newly generated neurons become established in the intermediate zone and project to the LOT; 2) the cells reorient and spread their dendrites at the same time as OSN axons penetrate the OB (this is a sensitive period between embryonic day (E)15-16, in which the arrival of afferents establishes a spatial and temporal gradient that facilitates protoglomerulus and glomerulus formation); and 3) final refinement of the radially orientated cells to adopt a mature morphology. These results suggest that both afferent inputs and intrinsic factors participate to produce the well-defined sensory system.

Maturation of the olfactory sensory neurons by Apaf-1/caspase-9–mediated caspase activity

“…During olfactory development, axons from early-born OSNs begin to penetrate the OB around embryonic day (E)14; these axons contact with projection neurons, mitral/tufted cells, at around E16 (10). We have previously found that a large number of OSNs with activated caspases were dispersed throughout the OE in late embryonic stage (Fig.…”

EphrinA5 protein distribution in the developing mouse brain

“…Glomeruli are designed as contact zone between growth cones of the primary olfactory neurons and dendrites of secondary olfactory neurons, known as mitral and tufted cells located in the olfactory bulb [35]. Primary olfactory neurons, mitral and tufted cells are neurons supporting early synaptic relays of the mouse olfactory system and so arise in a relatively parallel fashion between E9.5 and E10.5 [38]. In our study, we showed for the first time that the olfactory nerve expressed ephrinA5 in early embryogenesis (E12.5), suggesting either an involvement of this molecule in the guidance of primary olfactory neurons into the olfactory bulb or, an implication of ephrinA5 in the fasciculation of primary olfactory axons inside the olfactory nerve, possibly through an interaction with EphA4- and/or EphA5-receptors, shown to be expressed during embryogenesis in the olfactory nerve [35].…”

From the periphery to the brain: Wiring the olfactory system

“…These cells form a heterogeneous population expressing a different variety of markers as they migrate towards the CNS (see below). During these early stages, and despite the absence of a fully anatomically differentiated OB, projection neurons have already undergone generation and differentiation processes [49][50][51][52]. The close developmental timing between OE and OB raises the question whether the early OE axons play an inductive role in the OB protrusion and projection neurons' generation [53,54].…”