Spatially distinct functions of PAX6 and NKX2.2 during gliogenesis in the ventral spinal cord.
During ventral spinal cord (vSC) development, the p3 and pMN progenitor domain boundary is thought to be maintained by cross-repressive interactions between NKX2.2 and PAX6. Using loss-of-function analysis during the neuron-glial fate switch we show that the identity of the p3 domain is not maintained by the repressive function of NKX2.2 on Pax6 expression, even in the absence of NKX2.9. We further show that NKX2.2 is necessary to induce the expression of Slit1 and Sulfatase 1 (Sulf1) in the vSC in a PAX6-independent manner. Conversely, we show that PAX6 regulates Sulf1/Slit1 expression in the vSC in an NKX2.2/NKX6.1-independent manner. Consequently, deregulation of Sulf1 expression in Pax6-mutant embryos has stage-specific implications on neural patterning, associated with enhancement of Sonic Hedgehog activity. On the other hand, deregulation of Slit1 expression in gliogenic neural progenitors leads to changes in Astrocyte subtype identity. These data provide important insights into specific functions of PAX6 and NKX2.2 during glial cell specification that have so far remained largely unexplored.
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
Malas
Stavros
S
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins
D005136:Eye Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C000715627:Nkx2-2 protein, mouse; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; C120010:Slit1 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish; C486773:Sulf1 protein, mouse; D015238:Sulfotransferases