Transcription factors Nkx3.1 and Nkx3.2 (Bapx1) play an overlapping role in sclerotomal development of the mouse.
The homeobox containing transcription factors Nkx3.1 and Nkx3.2 (Bapx1) are transiently coexpressed in somites during early embryonic mouse development. Targeted disruption of the Nkx3.2 (Bapx1) gene in mice results in limited defects of chondrocranial bones and the axial skeleton, particularly pronounced in cervical vertebrae. In contrast, inactivation of the Nkx3.1 gene causes no apparent skeletal phenotype despite its early expression in sclerotomal cells. These observations suggested that both genes might fulfill partially overlapping functions during development of the vertebral column. To test this hypothesis we have generated Nkx3.1/Nkx3.2 double homozygous mutants. The simultaneous loss of both genes caused embryonic lethality between E12.5 and E17.5. Double mutants exhibited enhanced defects of vertebrae compared with Bapx1-deficient animals. In vertebral anlagen sclerotomal cells condensing around the notochord were almost completely lost during early embryogenesis of double null mutants. Defects appeared most severe in the cranial region and less prominent in thoracic and lumbar regions. The reduction of chondrogenic cells resulted in the incomplete formation of vertebral bodies, missing major parts of their ventro-medial aspects. The enhanced skeletal phenotype of double null mutants compared to the single Bapx1 mutation demonstrates that Nkx3.1 contributes to the formation of the axial skeleton in addition to the Bapx1 gene. Moreover, both genes seem to collaborate in a yet unknown vital function in the mouse embryo.
Herbrand
Heike
H
Department of Cell and Molecular Biology, Technical University of Braunschweig, Spielmann Street 7, 38106 Braunschweig, Germany.
Pabst
Oliver
O
Hill
Robert
R
Arnold
Hans-Henning
HH
D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics*; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D019170:Somites / Q000166:cytology / Q000378:metabolism*; D013131:Spine / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; C102837:Nkx3-1 protein, mouse; C107965:Nkx3-2 protein, mouse; D014157:Transcription Factors