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 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.
Department of Biology, American University of Beirut Beirut, Lebanon.
Carine
C
Jaafar
Department of Biology, American University of Beirut Beirut, Lebanon.
Saad
S
Omais
Department of Biology, American University of Beirut Beirut, Lebanon.
Sawsan
S
Al Lafi
Department of Biology, American University of Beirut Beirut, Lebanon.
Nadim
N
El Jamal
Department of Biology, American University of Beirut Beirut, Lebanon.
Mohammad
M
Noubani
Department of Biology, American University of Beirut Beirut, Lebanon.
Larissa
L
Skaf
Department of Biology, American University of Beirut Beirut, Lebanon.
Noël
N
Ghanem
Rb; axonal guidance; cell survival; neurogenesis; olfactory bulb; olfactory epithelium; signaling molecules
Stem Cell Rev. 2013 Dec;9(6):794-805
23900682
Mol Cell Biol. 2007 Jul;27(13):4825-43
17452454
J Comp Neurol. 2006 Jun 1;496(4):529-43
16572431
Annu Rev Cell Dev Biol. 2006;22:713-37
17029582
Dev Biol. 1980 Jan;74(1):205-15
7350009
Int J Dev Neurosci. 2014 Oct;37:76-86
25003986
J Neurosci. 1998 Nov 1;18(21):8919-27
9786997
J Neurosci. 2004 Jul 28;24(30):6676-85
15282270
EMBO J. 2005 Dec 21;24(24):4381-91
16308563
Neuron. 1993 Jun;10(6):1035-48
8318228
J Neurosci. 2012 Jun 13;32(24):8219-30
22699903
Development. 2009 May;136(9):1453-64
19297409
J Neurosci. 2012 Feb 29;32(9):2964-75
22378870
J Neurosci. 2007 Aug 22;27(34):9094-104
17715346
Stain Technol. 1983 Mar;58(2):121-2
6194583
Cell. 2010 Jun 11;141(6):1056-67
20550939
Semin Cell Dev Biol. 2006 Aug;17(4):462-70
16750923
J Neurosci. 2011 May 25;31(21):7920-6
21613506
J Comp Neurol. 1968 Nov;134(3):287-304
5721256
Mol Cell Biol. 2011 Jan;31(2):238-47
21059867
Cell Mol Neurobiol. 2006 Jul-Aug;26(4-6):803-21
16708285
Genes Dev. 2000 Apr 15;14(8):994-1004
10783170
J Neurosci. 2007 May 30;27(22):5926-35
17537963
Neuroscience. 1992;46(3):617-29
1545913
J Comp Neurol. 1997 Mar 10;379(2):171-84
9050783
Genes Dev. 2012 Jul 1;26(13):1409-20
22751497
J Comp Neurol. 1996 Feb 26;366(1):1-14
8866842
Cell Death Differ. 2002 Dec;9(12):1279-86
12478464
Hippocampus. 2016 Nov;26(11):1379-1392
27325572
Brain Res. 1987 Oct 20;424(1):144-52
2446705
Neuroscience. 1992 Jul;49(2):255-75
1436469
Behav Brain Res. 2012 Feb 14;227(2):480-9
21843557
J Neurosci. 2012 Oct 17;32(42):14809-14
23077065
J Neurosci. 2005 Apr 6;25(14):3586-92
15814789
Curr Opin Genet Dev. 2003 Oct;13(5):543-50
14550422
Cell Cycle. 2006 Jul;5(14):1506-13
16861920
Ann N Y Acad Sci. 2007 Dec;1121:87-101
17872397
J Comp Neurol. 1999 Oct 18;413(2):289-304
10524340
Glia. 2011 Feb;59(2):278-92
21125652
Development. 2016 May 1;143(9):1534-46
27143755
J Neurosci. 2008 Apr 16;28(16):4244-9
18417704
Sci Rep. 2016 Feb 05;6:20230
26847607
J Neurophysiol. 2004 Jun;91(6):2532-40
14960563
Cold Spring Harb Perspect Biol. 2010 Sep;2(9):a001933
20591992
J Neurosci. 2003 Jan 15;23(2):568-78
12533617
EMBO J. 2002 Jul 1;21(13):3337-46
12093735
J Neurocytol. 1979 Feb;8(1):1-18
438867
Development. 1999 Jul;126(13):2901-9
10357934
Neuron. 2000 Nov;28(2):411-25
11144352
Neuron. 1989 Jul;3(1):115-27
2482777
J Comp Neurol. 2000 Dec 18;428(3):511-26
11074448
Ann N Y Acad Sci. 1998 Nov 30;855:83-94
9929589
Mol Cell Neurosci. 2010 Jul;44(3):233-45
20363325
Dev Biol. 2012 Nov 15;371(2):269-79
22981605
Dev Biol. 2000 Jun 15;222(2):296-306
10837119