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Role of Rb during neurogenesis and axonal guidance in the developing olfactory system

Title: Role of Rb during neurogenesis and axonal guidance in the developing olfactory system
Authors: Carine Jaafar; Saad Omais; Sawsan Al Lafi; Nadim El Jamal; Mohammad Noubani; Larissa Skaf; Noël Ghanem
Source: Frontiers in Molecular Neuroscience, Vol 9 (2016)
Publisher Information: Frontiers Media S.A.
Publication Year: 2016
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: Cell Survival; Neurogenesis; Olfactory Bulb; Axonal guidance; signaling molecules; olfactory epithelium; Neurosciences. Biological psychiatry. Neuropsychiatry; RC321-571
Description: The Retinoblastoma protein, Rb, was shown to regulate distinct aspects of neurogenesis in the embryonic and adult brain besides its primary role in cell cycle control. It is still unknown, however, whether Rb is required for tissue morphogenesis and the establishment of synaptic connections between adjacent tissues during development. We have investigated here the role of Rb during development of the olfactory system (OS), which heavily relies on reciprocal interactions between the olfactory epithelium (OE) and the olfactory bulb (OB). We show that mice carrying a telencephalic-specific deletion of Rb display several neurogenic defects in the OS during late development. In the OE, loss of Rb leads to ectopic proliferation of late-born progenitors (Tuj-1+), abnormal radial migration and terminal maturation of olfactory sensory neurons (OSNs). In the OB, deletion of Rb causes severe lamination defects with loss of clear boundaries between distinct layers. Importantly, starting around E15.5 when OB glomerulogenesis is initiated, many OSNs axons that project along the olfactory nerve layer (ONL) fail to properly innervate the nascent bulb, thus resulting in partial loss of connectivity between OE-OB and gradual neuronal degeneration in both tissues peaking at birth. This deficiency correlates with deregulated expressions of two key chemo-repellant molecules, Robo2/Slit1 and Nrp2/sema3F that control the formation of dorsal-ventral topographic map of OSNs connections with OB glomeruli. This study highlights a critical requirement for Rb during neurogenesis and the establishment of proper synaptic connections inside the OS during development.
Document Type: article in journal/newspaper
Language: English
Relation: http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00081/full; https://doaj.org/toc/1662-5099; https://doaj.org/article/ca78c323ce1c43189d7b6fa71bd34a7a
DOI: 10.3389/fnmol.2016.00081
Availability: https://doi.org/10.3389/fnmol.2016.00081; https://doaj.org/article/ca78c323ce1c43189d7b6fa71bd34a7a
Accession Number: edsbas.BC3EB37E
Database: BASE