title: Sp8 plays a supplementary role to Pax6 in establishing the pMN/p3 domain boundary in the spinal cord.
abstract: Progenitor cells are segregated into multiple domains along the dorsoventral axis of the vertebrate neural tube, and each progenitor domain generates particular types of neurons. Selective cross-repressive interactions between pairs of class I and class II transcription factors play important roles in patterning neural progenitors into domains with clear boundaries. Here, we provide evidence that the zinc-finger protein Sp8 plays a supplementary role to Pax6 in establishing the pMN/p3 domain boundary through mutually repressive interactions with the class II protein Nkx2-2. The ventral limit of Sp8 expression is complementary to the dorsal limit of Nkx2-2 expression at the pMN/p3 boundary. Sp8 and Nkx2-2 exert cross-repressive interactions, and changing the expression of Sp8 and Nkx2-2 is coupled with pMN and p3 progenitor fate conversion. Sp8 exerts its neural patterning activities by acting as a transcriptional activator. The expression of a repressive form of Sp8 results in the selective inhibition of motor neuron generation and the ectopic induction of Nkx2-2 expression. Sp8 expression is positively regulated by, but not completely dependent on, Pax6. Furthermore, whereas loss of Pax6 function alone results in disruption of the pMN/p3 domain boundary only in the rostral levels of the spinal cord, loss of both Sp8 and Pax6 functions results in disruption of the pMN/p3 domain boundary along the whole rostrocaudal axis of the spinal cord. We conclude that Sp8 plays a supplementary role to Pax6 in specifying the pMN over p3 progenitor fate through cross-repressive interactions with Nkx2-2.
authors.affiliation: Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China 072023029@fudan.edu.cn yangz@fudan.edu.cn.
authors.forename: Xiaosu
authors.initials: X
authors.lastname: Li
authors.affiliation: Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou 310036, China Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY40392, USA.
authors.forename: Mengsheng
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China 072023029@fudan.edu.cn yangz@fudan.edu.cn.
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008938:Mitosis; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism*; D029961:Zebrafish Proteins
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715631:NKX2-2 protein, human; C000715627:Nkx2-2 protein, mouse; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; C490035:Sp8 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish
keywords: Chick; Motor neuron; Mouse; Nkx2-2; Pax6; Sp8; Ventral patterning