Abnormal development of the thoracic skeleton in mice homozygous for the gene for looped‐tail

Stein, Kathryn F.; Mackensen, Judith A.

doi:10.1002/aja.1001000203

Cited by 32 publications

(8 citation statements)

References 23 publications

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“…The Vangl2 Lp/Lp mutant is characterised by a wide neural tube with a broad floor plate and also has vertebral abnormalities (Greene et al, 1998;Stein and Mackensen, 1957). Consistent with previous analysis, we found that the lumbar vertebral bodies are not split, although a few split anterior thoracic vertebrae that are also fused along the anterior-posterior axis were observed ( Fig.…”

Section: Dchs1 Mutantssupporting

confidence: 81%

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Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae

et al. 2016

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The protocadherins Fat4 and Dchs1 act as a receptor-ligand pair to regulate many developmental processes in mice and humans, including development of the vertebrae. Based on conservation of function between Drosophila and mammals, Fat4-Dchs1 signalling has been proposed to regulate planar cell polarity (PCP) and activity of the Hippo effectors Yap and Taz, which regulate cell proliferation, survival and differentiation. There is strong evidence for Fat regulation of PCP in mammals but the link with the Hippo pathway is unclear. In Fat4 −/− and Dchs1 −/− mice, many vertebrae are split along the midline and fused across the anterior-posterior axis, suggesting that these defects might arise due to altered cell polarity and/or changes in cell proliferation/differentiation. We show that the somite and sclerotome are specified appropriately, the transcriptional network that drives early chondrogenesis is intact, and that cell polarity within the sclerotome is unperturbed. We find that the key defect in Fat4 and Dchs1 mutant mice is decreased proliferation in the early sclerotome. This results in fewer chondrogenic cells within the developing vertebral body, which fail to condense appropriately along the midline. Analysis of Fat4;Yap and Fat4;Taz double mutants, and expression of their transcriptional target Ctgf, indicates that Fat4-Dchs1 regulates vertebral development independently of Yap and Taz. Thus, we have identified a new pathway crucial for the development of the vertebrae and our data indicate that novel mechanisms of Fat4-Dchs1 signalling have evolved to control cell proliferation within the developing vertebrae.

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Section: Dchs1 Mutantssupporting

confidence: 81%

“…Consistent with previous analysis, we found that the lumbar vertebral bodies are not split, although a few split anterior thoracic vertebrae that are also fused along the anterior-posterior axis were observed ( Fig. 3D; data not shown) (see also Greene et al, 1998;Stein and Mackensen, 1957).…”

Section: Dchs1 Mutantssupporting

confidence: 80%

Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae

et al. 2016

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“…A number of studies of Loop-tail embryos have concluded that there are various abnormalities related to axial elongation, (12) including fewer mitotic spindles in the neural tube that are oriented in a longitudinal direction. (13) Stein and Rudin (14) did not observe any abnormalities in mesodermal or notochord structures in homozygotes, but did find excessive mitoses in the brain region. The formation of the floor plate, and thus the medial hinge point, is clearly abnormal in Lp/Lp embryos.…”

Section: Mechanisms Of Neural Tube Closurementioning

confidence: 89%

Identification of the mouse Loop‐tail gene: a model for human craniorachischisis?

Kapron

2002

BioEssays

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Neural tube defects are one of the commonest human birth defects, with more than 0.5% of some populations affected. Mouse models are being used in an attempt to identify genes that could be involved in these malformations. Only two mouse mutations are known to lead to craniorachischisis, failure of closure of almost the entire neural tube. Two recent papers report that the gene for one of these, Loop-tail, has now been identified and sequenced.1, 2 It has been given the designation Ltap/Lpp1 and appears to function in floor plate formation. It will be of great interest to investigate the role of this gene in human neural tube defects.

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“…[84][85] Lp heterozygotes are characterized by a "looped" tail appearance, while homozygotes develop a severe NTD resembling human craniorachischisis. [86] NTD in Lp is caused by independent missense mutations S464N (Lp) and D255E (Lpm1Jus), localized in the proposed C-terminal cytoplasmic domain of a gene, now referred to as Van Gogh-like 2 (Vangl2). [84-85; 87] A novel experimentally induced allele, Lp (m2Jus), having a missense mutation, R259L, in Vangl2 has been recently reported.…”

Section: Genes Of Pcp Pathway and Ntdsmentioning

confidence: 99%

Advances in Genetics of Non Syndromic Neural Tube Defects

Marco¹

2012

Neural Tube Defects - Role of Folate, Prevention Strategies and Genetics

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Abnormal development of the thoracic skeleton in mice homozygous for the gene for looped‐tail

Cited by 32 publications

References 23 publications

Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae

Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae

Identification of the mouse Loop‐tail gene: a model for human craniorachischisis?

Advances in Genetics of Non Syndromic Neural Tube Defects

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