Hypomorphic Mesp allele distinguishes establishment of rostrocaudal polarity and segment border formation in somitogenesis.
A bHLH-type transcription factor, Mesp2, plays an essential role in somite segmentation in mice. Zebrafish mespb (mesp-b), a putative homologue of mouse Mesp2, is transiently expressed in the rostral presomitic mesoderm similarly to Mesp2. To determine whether zebrafish mespb is a functional homologue of mouse Mesp2, zebrafish mespb was introduced into the mouse Mesp2 locus by homologous recombination. Introduced mespb almost rescued the Mesp2 deficiency in the homozygous mespb knockin mouse, indicating that mespb is a functional homologue of mouse Mesp2. Segmented somites were clearly observed although the partial fusion of the vertebral columns still occurred. Interestingly, however, the nature and dosage of the mespb gene affected the rescue event. A mouse line, which has a hypomorphic Mesp2 allele generated by the introduction of neo-mespb, gave rise to an epithelial somite without normal rostrocaudal (RC) polarity. RC polarity was also lacking in the presomitic mesoderm. The defects in RC polarity were determined by the altered expressions of Uncx4.1 and Dll1 in the segmented somites and presomitic mesoderm, respectively. In contrast, the expression of EphA4 (Epha4), lunatic fringe or protocadherin, thought to be involved in segment border formation, was fairly normal in hypomorphic mutant embryos. These results suggest that the Mesp family of transcription factors is involved in both segment border formation and establishment of RC polarity through different genetic cascades.
Nomura-Kitabayashi
Aya
A
Cellular and Molecular Toxicology Division, National Institute of Health Sciences, 1-18-1 Kamiyohga, Setagaya-ku, Tokyo 158-8501, Japan.
Takahashi
Yu
Y
Kitajima
Satoshi
S
Inoue
Tohru
T
Takeda
Hiroyuki
H
Saga
Yumiko
Y
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D005260:Female; D005326:Fetal Proteins / Q000235:genetics; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D016695:Glycosyltransferases / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D000091363:Protocadherins; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D036122:Receptor, EphA4; D017386:Sequence Homology, Amino Acid; D019170:Somites; D013116:Spinal Cord / Q000002:abnormalities; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D005326:Fetal Proteins; D016695:Glycosyltransferases; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000091363:Protocadherins; D020794:Receptor Protein-Tyrosine Kinases; D036122:Receptor, EphA4; D014157:Transcription Factors; D029961:Zebrafish Proteins; C107407:Mesp2 protein, mouse; C115816:PCDH8 protein, human; C497204:Pcdh8 protein, mouse; C108545:Uncx4.1 protein, mouse; C064045:delta protein; C410085:mespba protein, zebrafish; C498393:LFNG protein, human; C498392:Lfng protein, mouse; C498390:lfng protein, zebrafish