title: Nato3 plays an integral role in dorsoventral patterning of the spinal cord by segregating floor plate/p3 fates via Nkx2.2 suppression and Foxa2 maintenance.
abstract: During embryogenesis, the dorsal roof plate and the ventral floor plate (FP) act as organizing centers to pattern the developing neural tube. Organizer-secreted morphogens provide signals that are interpreted via the graded expression of transcription factors. These factors establish a combinatorial code, which subsequently determines the fate of neuronal progenitors along the dorsoventral axis. To further separate the fates and promote distinct identities of the neural progenitors, mutual repression takes place among transcription factors expressed in progenitors situated along the dorsoventral axis. The molecular mechanisms acting in the developing spinal cord and underlying the segregation of the progenitor pool containing cells with a mixed FP/p3 fate into separate FP cells and V3 neurons are not fully understood. Using in vivo ectopic expression in chick, we found that Nato3 induces ectopic Foxa2-positive cells and indirectly downregulates Nkx2.2 expression. To examine the role of Nato3 in the FP, Foxa2-Nato3 signaling was blocked in Nato3 null mice and to a greater extent in Nato3 null/Foxa2 heterozygous bigenic mutants. Complementary to the findings obtained by gain of function in chick, the loss of function in mouse indicated that the segregation of the FP/p3 population into its derivatives was interrupted. Together, the data suggest that Nato3 is a novel determinant factor regulating the segregation of the FP and p3 identities, which is an essential step for establishing a definitive FP fate in the embryonic spinal cord.
authors.affiliation: Department of Cell and Developmental Biology, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Abed AlFatah
authors.initials: AA
authors.lastname: Mansour
authors.forename: Sophie
authors.initials: S
authors.lastname: Khazanov-Zisman
authors.forename: Yaara
authors.initials: Y
authors.lastname: Netser
authors.forename: Avihu
authors.initials: A
authors.lastname: Klar
authors.forename: Nissim
authors.initials: N
authors.lastname: Ben-Arie
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism*; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D054259:Neural Tube / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins
chemical_list: D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C000715627:Nkx2-2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish; D051542:Hepatocyte Nuclear Factor 3-beta
keywords: Chick in ovo electroporation; Ferd3l; Floor plate; Knockout mouse; Spinal cord development; bHLH transcription factor