Mesp2 initiates somite segmentation through the Notch signalling pathway

Takahashi, Yu; Koizumi, Ken-ichi; Takagi, Atsuya; Kitajima, Satoshi; Inoue, Tohru; Koseki, Haruhiko; Saga, Yumiko

doi:10.1038/78062

Cited by 199 publications

(227 citation statements)

References 28 publications

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“…Somites were formed in regular time intervals, but the presumptive, nascent, and newly formed somites of the mutant were smaller, as reflected by reduction of Mesp2 and Cer1. Consistent with the role of Mesp2 in initiation of somite segmentation and formation of the anterior half of the somite, Mesp2-null embryos show severe somite defects due to a lack of the rostral somitic compartment (Takahashi et al, 2000).…”

Section: Ror2 Is Essential For Somite Formationsupporting

confidence: 60%

Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome

Schwabe

Trepczik

Süring

et al. 2004

Developmental Dynamics

122

113

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Robinow syndrome (RS) is a human dwarfism syndrome characterized by mesomelic limb shortening, vertebral and craniofacial malformations and small external genitals. We have analyzed Ror2 -/-mice as a model for the developmental pathology of RS. Our results demonstrate that vertebral malformations in Ror2 -/-mice are due to reductions in the presomitic mesoderm and defects in somitogenesis. Mesomelic limb shortening in Ror2 -/-mice is a consequence of perturbed chondrocyte differentiation. Moreover, we show that the craniofacial phenotype is caused by a midline outgrowth defect. Ror2 expression in the genital tubercle and its reduced size in Ror2 -/-mice makes it likely that Ror2 is involved in genital development. In conclusion, our findings suggest that Ror2 is essential at multiple sites during development. The Ror2 -/-mouse provides a suitable model that may help to explain many of the underlying developmental malformations in individuals with Robinow syndrome. Developmental Dynamics 229: 400 -410, 2004.

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Section: Ror2 Is Essential For Somite Formationsupporting

confidence: 60%

Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome

Schwabe

Trepczik

Süring

et al. 2004

Developmental Dynamics

122

113

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“…In murine somitogenesis, MesP2 has a key role in establishing rostrocaudal polarity by participating in distinct Notch-signaling pathways (Takahashi et al, 2000(Takahashi et al, , 2003. Mesp2 expression is induced by Dll1-mediated Notch signaling (presenilin1-independent) and Dll3-mediated Notch signaling (presenilin1-dependent), while inhibition of Mesp2 expression is achieved through presenilin1-independent Dll3-Notch signaling.…”

Section: Mesoderm Posterior 2 (Mesp2)mentioning

confidence: 99%

Abnormal vertebral segmentation and the notch signaling pathway in man

Turnpenny

Alman

Cornier

et al. 2007

Developmental Dynamics

145

120

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Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal models. Nevertheless, some spectacular advances in the cell biology and molecular genetics of somitogenesis in animal models have proved to be directly relevant to human disease. Some advances in our understanding have come through DNA linkage analysis in families demonstrating a clustering of AVS cases, as well as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear Mendelian inheritance, but three genes-DLL3, MESP2, and LNFG-have now been identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of fusion. In familial cases clearly following a Mendelian pattern, autosomal recessive inheritance is more common than autosomal dominant and the genes identified are functional within the Notch signaling pathway. Other genes within the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. Here, we deal mainly with SCD and AGS, and present a new classification system for AVS phenotypes, for which, hitherto, the terminology has been inconsistent and confusing.

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“…Signaling within and between these stabilized cohorts of cells subsequently refines the anterior and posterior domains of the presumptive somite. Formation of these stripes is manifested in domain-specific expression of genes such as mouse Mesp1 and Mesp2 (Takahashi et al 2000), zebrafish mesp-a and mesp-b Sawada et al 2000a), and mouse Delta-like1 (Dll1) (Bettenhausen et al 1995) or ephrinB2 (Holder and Klein 1999;Holder et al 2000). The helix-loop-helix transcription factor Mesp appears to be important for the anterior-posterior regionalization of somite primordia, and this process is thought to be essential for boundary formation Sawada et al 2000b;Takahashi et al 2000).…”

mentioning

confidence: 99%

“…Formation of these stripes is manifested in domain-specific expression of genes such as mouse Mesp1 and Mesp2 (Takahashi et al 2000), zebrafish mesp-a and mesp-b Sawada et al 2000a), and mouse Delta-like1 (Dll1) (Bettenhausen et al 1995) or ephrinB2 (Holder and Klein 1999;Holder et al 2000). The helix-loop-helix transcription factor Mesp appears to be important for the anterior-posterior regionalization of somite primordia, and this process is thought to be essential for boundary formation Sawada et al 2000b;Takahashi et al 2000). Formation of the boundary between the posterior of the forming somite and the anterior of the next-to-beformed presumptive somite involves the correct expression in the mesoderm of a number of evolutionarily conserved genes, as well as signals, not yet identified, from the ectoderm (Sosic et al 1997;Correia and Conlon 2000).…”

mentioning

confidence: 99%

The winged helix transcription factor Foxc1a is essential for somitogenesis in zebrafish

et al. 2001

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Previous studies identified zebrafish foxc1a and foxc1b as homologs of the mouse forkhead gene, Foxc1. Both genes are transcribed in the unsegmented presomitic mesoderm (PSM), newly formed somites, adaxial cells, and head mesoderm. Here, we show that inhibiting synthesis of Foxc1a (but not Foxc1b) protein with two different morpholino antisense oligonucleotides blocks formation of morphological somites, segment boundaries, and segmented expression of genes normally transcribed in anterior and posterior somites and expression of paraxis implicated in somite epithelialization. Patterning of the anterior PSM is also affected, as judged by the absence of mesp-b, ephrinB2, and ephA4 expression, and the down-regulation of notch5 and notch6. In contrast, the expression of other genes, including mesp-a and papc, in the anterior of somite primordia, and the oscillating expression of deltaC and deltaD in the PSM appear normal. Nevertheless, this expression is apparently insufficient for the maturation of the presumptive somites to proceed to the stage when boundary formation occurs or for the maintenance of anterior/posterior patterning. Mouse embryos that are compound null mutants for Foxc1 and the closely related Foxc2 have no morphological somites and show abnormal expression of Notch signaling pathway genes in the anterior PSM. Therefore, zebrafish foxc1a plays an essential and conserved role in somite formation, regulating both the expression of paraxis and the A/P patterning of somite primordia.

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Mesp2 initiates somite segmentation through the Notch signalling pathway

Cited by 199 publications

References 28 publications

Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome

Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome

Abnormal vertebral segmentation and the notch signaling pathway in man

The winged helix transcription factor Foxc1a is essential for somitogenesis in zebrafish

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