Del(10)(q22.3q24.1) associated with juvenile polyposis

Jacoby, Russell F.; Schlack, Steven; Sekhon, Gurbax S.; Laxová, Renata

doi:10.1002/(sici)1096-8628(19970627)70:4<361::aid-ajmg6>3.0.co;2-w

Cited by 48 publications

(21 citation statements)

References 27 publications

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“…Furthermore, these patients and our double-tg mice both suffer from similar heart septal defects (Delnatte et al, 2006; Jacoby et al, 1997; Menko et al, 2008; Zhou et al, 2001). Thus, facial abnormalities and heart septal defects in human patients might be partly caused by the knockdown of BMPR1A-mediated signaling in NC-derived cells.…”

Section: Discussionmentioning

confidence: 74%

Facial dysmorphism induced by bone morphogenetic protein receptor type 1A-mediated signaling reduction in neural crest-derived cells

Saito

Yamamura

Suzuki

2012

Disease Models &Amp; Mechanisms

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SUMMARYBone morphogenetic protein (BMP) receptor type 1A (BMPR1A) mutations are associated with facial dysmorphism, which is one of the main clinical signs in both juvenile polyposis and chromosome 10q23 deletion syndromes. Craniofacial development requires reciprocal epithelial/neural crest (NC)-derived mesenchymal interactions mediated by signaling factors, such as BMP, in both cell populations. To address the role of mesenchymal BMP signaling in craniofacial development, we generated a conditional knockdown mouse by expressing the dominant-negative Bmpr1a in NC-derived cells expressing the myelin protein zero(Mpz)-Cre transgene. At birth, 100% of the conditional mutant mice had wide-open anterior fontanelles, and 80% of them died because of cleft face and cleft palate soon after birth. The other 20% survived and developed short faces, hypertelorism and calvarial foramina. Analysis of the NC-derived craniofacial mesenchyme of mutant embryos revealed an activation of the P53 apoptosis pathway, downregulation of both c-Myc and Bcl-XL, a normal growth rate but an incomplete expansion of mesenchymal cells. These findings provide genetic evidence indicating that optimal Bmpr1a-mediated signaling is essential for NC-derived mesenchymal cell survival in both normal nasal and frontal bone development and suggest that our model is useful for studying some aspects of the molecular etiology of human craniofacial dysmorphism.

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Section: Discussionmentioning

confidence: 74%

Facial dysmorphism induced by bone morphogenetic protein receptor type 1A-mediated signaling reduction in neural crest-derived cells

Saito

Yamamura

Suzuki

2012

Disease Models &Amp; Mechanisms

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“…Stromal fibroblasts unresponsive to TGF-b generated HGF and this abnormal paracrine signaling lead to epithelial tumors (Bhowmick et al, 2004;Radisky and Bissell, 2004). Furthermore, stromal defects occur in a number of hereditary gastrointestinal cancers such as juvenile polyposis, where Smad4 and BMP2R mutations account for over 30% of cases (Jacoby et al, 1997;Howe et al, 1998). In these examples, the TGF-b pathway acts as a powerful tumor suppressor, even in the presence of strong oncogene expression (Sternlicht et al, 1999).…”

Section: Capacities For Tissue Contributions Across Germ Layers In Thmentioning

confidence: 99%

The role of TGF-β and Wnt signaling in gastrointestinal stem cells and cancer

et al. 2005

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“…BmprIa deficiency in CNC lineage also arrested tooth development at the bud/cap stage associated with decreased levels of cell proliferation and down-regulation of several BMP downstream genes in the dental mesenchyme [13]. Interestingly, in a dominant-negative transgenic mouse model, it was shown that reduced BMPRIa-mediated signaling caused facial dysmorphism and cleft palate, mimicking the hypertelorism and flat nasal bridge observed in patients with juvenile polyposis syndrome and chromosome 10q23 deletion syndrome that are associated with BMPRIA mutations or deletion [27], [28], [29], [30], [31]. The indispensable role of BmprIa is further supported by the fact that BmprIb has limited redundant function with BmprIa in tooth and palate development [13].…”

Section: Introductionmentioning

confidence: 96%

Augmented BMPRIA-Mediated BMP Signaling in Cranial Neural Crest Lineage Leads to Cleft Palate Formation and Delayed Tooth Differentiation

Wang

Lin

et al. 2013

PLoS ONE

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The importance of BMP receptor Ia (BMPRIa) mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa) in cranial neural crest (CNC) cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.

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Del(10)(q22.3q24.1) associated with juvenile polyposis

Cited by 48 publications

References 27 publications

Facial dysmorphism induced by bone morphogenetic protein receptor type 1A-mediated signaling reduction in neural crest-derived cells

Facial dysmorphism induced by bone morphogenetic protein receptor type 1A-mediated signaling reduction in neural crest-derived cells

The role of TGF-β and Wnt signaling in gastrointestinal stem cells and cancer

Augmented BMPRIA-Mediated BMP Signaling in Cranial Neural Crest Lineage Leads to Cleft Palate Formation and Delayed Tooth Differentiation

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