SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch.
During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial (Nu/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.
Genethliou
Nicholas
N
The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia, Cyprus.
Panayiotou
Elena
E
Panayi
Helen
H
Orford
Michael
M
Mean
Richard
R
Lapathitis
George
G
Gill
Herman
H
Raoof
Sahir
S
De Gasperi
Rita
R
Elder
Gregory
G
Kessaris
Nicoletta
N
Richardson
William D
WD
Malas
Stavros
S
D000818:Animals; D019521:Body Patterning; D000090322:Homeobox Protein Nkx-2.2; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development*
D000090322:Homeobox Protein Nkx-2.2; C000715627:Nkx2-2 protein, mouse; D051880:Receptors, Notch; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse