spiel ohne grenzen/pou2 is required for zebrafish hindbrain segmentation.
Segmentation of the vertebrate hindbrain leads to the formation of a series of rhombomeres with distinct identities. In mouse, Krox20 and kreisler play important roles in specifying distinct rhombomeres and in controlling segmental identity by directly regulating rhombomere-specific expression of Hox genes. We show that spiel ohne grenzen (spg) zebrafish mutants develop rhombomeric territories that are abnormal in both size and shape. Rhombomere boundaries are malpositioned or absent and the segmental pattern of neuronal differentiation is perturbed. Segment-specific expression of hoxa2, hoxb2 and hoxb3 is severely affected during initial stages of hindbrain development in spg mutants and the establishment of krx20 (Krox20 ortholog) and valentino (val; kreisler ortholog) expression is impaired. spg mutants carry loss-of-function mutations in the pou2 gene. pou2 is expressed at high levels in the hindbrain primordium of wild-type embryos prior to activation of krx20 and val. Widespread overexpression of Pou2 can rescue the segmental krx20 and val domains in spg mutants, but does not induce ectopic expression of these genes. This suggests that spg/pou2 acts in a permissive manner and is essential for normal expression of krx20 and val. We propose that spg/pou2 is an essential component of the regulatory cascade controlling hindbrain segmentation and acts before krx20 and val in the establishment of rhombomere precursor territories.
Hauptmann
Giselbert
G
Albert-Ludwigs-Universität Freiburg, Institut für Biologie I, Hauptstrasse 1, D-79104 Freiburg i. Br., Germany.
Belting
Heinz-Georg
HG
Wolke
Uta
U
Lunde
Karen
K
Söll
Iris
I
Abdelilah-Seyfried
Salim
S
Prince
Victoria
V
Driever
Wolfgang
W
D000818:Animals; D030801:Animals, Genetically Modified; D030161:Avian Proteins; D019521:Body Patterning / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D051767:Early Growth Response Protein 2; D005326:Fetal Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D050977:Maf Transcription Factors; D051258:MafB Transcription Factor; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D050814:Octamer Transcription Factor-3; D015513:Oncogene Proteins; D050809:POU Domain Factors; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D036122:Receptor, EphA4; D012249:Rhombencephalon / Q000196:embryology*; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics*; D029867:Xenopus Proteins; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D005326:Fetal Proteins; D018398:Homeodomain Proteins; C078105:Hox 2.7 protein, Xenopus; C489830:Hoxa2 protein, Xenopus; C489833:Hoxa2 protein, mouse; C080331:Hoxa3 protein, mouse; C490111:Hoxb2 protein, mouse; D050977:Maf Transcription Factors; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D009419:Nerve Tissue Proteins; D050814:Octamer Transcription Factor-3; D015513:Oncogene Proteins; D050809:POU Domain Factors; C490059:POU3F4 protein, Xenopus; C085437:Pou5f3 protein, zebrafish; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C489831:hoxa2b protein, zebrafish; C111092:mafb protein, zebrafish; C490408:mafbb protein, zebrafish; D020794:Receptor Protein-Tyrosine Kinases; D036122:Receptor, EphA4