Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System

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...

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Main Authors:	Jaafar, Carine, Omais, Saad, Al Lafi, Sawsan, El Jamal, Nadim, Noubani, Mohammad, Skaf, Larissa, Ghanem, Noël
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016521/

id	pubmed-5016521
recordtype	oai_dc
spelling	pubmed-50165212016-09-23 Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System Jaafar, Carine Omais, Saad Al Lafi, Sawsan El Jamal, Nadim Noubani, Mohammad Skaf, Larissa Ghanem, Noël Neuroscience 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. Frontiers Media S.A. 2016-09-09 /pmc/articles/PMC5016521/ /pubmed/27667971 http://dx.doi.org/10.3389/fnmol.2016.00081 Text en Copyright © 2016 Jaafar, Omais, Al Lafi, El Jamal, Noubani, Skaf and Ghanem. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Jaafar, Carine Omais, Saad Al Lafi, Sawsan El Jamal, Nadim Noubani, Mohammad Skaf, Larissa Ghanem, Noël
spellingShingle	Jaafar, Carine Omais, Saad Al Lafi, Sawsan El Jamal, Nadim Noubani, Mohammad Skaf, Larissa Ghanem, Noël Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System
author_facet	Jaafar, Carine Omais, Saad Al Lafi, Sawsan El Jamal, Nadim Noubani, Mohammad Skaf, Larissa Ghanem, Noël
author_sort	Jaafar, Carine
title	Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System
title_short	Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System
title_full	Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System
title_fullStr	Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System
title_full_unstemmed	Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System
title_sort	role of rb during neurogenesis and axonal guidance in the developing olfactory system
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.
publisher	Frontiers Media S.A.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016521/
_version_	1613646793217671168

Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System

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