Mesenchymal patterning by<i>Hoxa2</i>requires blocking Fgf-dependent activation of<i>Ptx1</i>

Bobola, Nicoletta; Carapuço, Marta; Ohnemus, Sabine; Kanzler, Benoı̂t; Leibbrandt, Andreas; Neubüser, Annette; Drouin, Jacques; Mallo, Moisés

doi:10.1242/dev.00554

Cited by 39 publications

(43 citation statements)

References 47 publications

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“…The frequency of embryos displaying a phenotype (7 of 27, i.e., 26%) is consistent with our previous use of the Msx2 promoter fragment to target expression of heterologous cDNAs (transgene expression detected in 25-30% of transgenic embryos) and is therefore a likely consequence of the intrinsic activity of the Msx2 promoter (Bobola et al, 2003;Kutejova et al, 2005). Together, these results show that ectopic expression of Igfbp5 can interfere with the normal growth of craniofacial bones.…”

Section: Igfbp5 Has a Negative Effect On Bone Formationsupporting

confidence: 89%

IGFBP5 is a potential regulator of craniofacial skeletogenesis

Bobola

Engist

2008

Genesis

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Summary: Six known proteins bind to the insulin-like growth factor (IGF) with high affinity. Igfbp5 encodes one of these proteins, which regulates the activity of IGF, but also exerts IGF-independent actions. Using in situ hybridization to detect cells expressing Igfbp5 mRNA, we show that Igfbp5 is expressed in a dynamic pattern in the mouse embryonic craniofacial region. At early stages corresponding to the completion of neural crest migration, Igfbp5 mRNA was found predominantly in the epithelia, whereas when the craniofacial mesenchyme has begun its differentiation into skeletal tissue, Igfbp5-expressing cells surrounded the developing cartilages and bones. Embryos transgenically expressing Igfbp5 in restricted areas of the mesenchyme fated to form craniofacial bones revealed decreased ossification and even deletion of head bones areas. Transgenic expression of a mutant Igfbp5, encoding a product with reduced binding affinity for IGF, led to no skeletal abnormalities, suggesting that the observed negative effects on skeletal development rely on a mechanism that depends on binding to IGF. genesis 46:52-59, 2008.

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Section: Igfbp5 Has a Negative Effect On Bone Formationsupporting

confidence: 89%

IGFBP5 is a potential regulator of craniofacial skeletogenesis

Bobola

Engist

2008

Genesis

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“…It is unclear why the increased expressions of the 4 HOX genes are of advantage to metastasize; however, we speculate as follows. It is known that the expressions of HOXA1 and A2 are regulated by growth hormone and growth factors belonging to the fibroblast growth factor (FGF) family, respectively, 12,20 and that melanoma expresses growth hormone receptors and FGF receptors. [21][22][23] Therefore, the microenvironment including such hormones and growth factors may promote metastasis via changes of some HOX gene expressions.…”

Section: Discussionmentioning

confidence: 99%

Altered expressions of HOX genes in human cutaneous malignant melanoma

Maeda

Hamada

Takahashi

et al. 2004

Intl Journal of Cancer

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HOX genes act as master genes to control morphogenesis. In human, HOX genes form 4 clusters composing 9 to 11 HOX genes (39 genes in total) on different chromosomes. We hypothesized that aberrant expression of HOX genes was associated with development and subsequent progression of melanoma and that the 39 HOX gene expression pattern determined the sites where melanoma grew. The expression levels of 39 HOX genes in 15 human cutaneous melanoma specimens and 7 nevus pigmentosus specimens were quantified by a comprehensive analysis system based on the real-time RT-PCR method. We found that the expression levels of HOXA11, A13, B9, D12 and D13 in melanoma were higher than those in nevus pigmentosus and that the expression levels of HOXA11, B2 and C13 were significantly different between pT4 melanoma and pT1 to pT3 melanoma. It was most notable that the expression levels of HOXA1, A2, C4 and B13 in melanoma with distant metastasis were higher than those in melanoma without it. On the other hand, we found no relationship between HOX genes expression patterns and the growing sites of melanoma. These results indicated that the misexpressions of some specific HOX genes were implicated in melanoma genesis and metastasis but had no linkage with melanoma sites. © 2004 Wiley-Liss, Inc. Key words: melanoma; HOX; metastasis; nevus pigmentosusHox genes are one of the master regulators of morphogenesis and cell differentiation during embryogenesis of animals. 1 The genes contain a 180 bp DNA sequence (homeobox), which encodes a highly conserved 60 amino acid homeodomain. The HOX proteins function as transcription factors through their homeodomain, which is responsible for recognition and binding of sequence-specific DNA motifs. 2,3 In human genome, 39 HOX genes are clustered in a similar arrangement of 13 paralog groups in 4 different chromosomal regions, HOXA, B, C and D. 4 During embryonic morphogenesis, the HOX genes determine positional identity along the anterior-posterior and secondary axes in animals. Within each cluster, HOX genes located at the 3Ј extremity are activated first and in anterior embryonic domains, whereas 5Ј-located genes are transcribed subsequently and in more caudal areas, which is the property called colinearity rule. 5 HOX genes are also expressed in some normal adult organs in characteristic patterns, suggesting their possible role in the maintenance of tissuespecific architecture besides their roles in embryogenesis. 6 -9 Comparative analysis of HOX gene expression between cancerous tissues and normal tissues uncovered the dysregulated expression(s) of a particular HOX gene(s) in some kinds of carcinomas. For example, HOXB5 and B9 are expressed in normal kidney but not in renal cancer, whereas the expression of HOXC11 is observed in human renal cancer but not in normal kidney. 6 In human prostate cancer, overexpression of HOXC8 correlates with loss of differentiated phenotype. 10 Increased expressions of HOXC4, C5, C6 and C11 are likely to be involved in the development of human bladder transitiona...

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“…CNCCs of the proximal mandibular prominence appear more sensitive to variations in the genetic environment, than are distal ones: inactivation or allelic reductions of Edn1, Ednra, Dlx5 (Acampora et al, 1999;Depew et al, 1999), Dlx6 (Jeong et al, 2008), Gsc (Yamada et al, 1995), Pitx1 (Bobola et al, 2003;Lanctot et al, 1999), Gbx2 (Byrd and Meyers, 2005) all lead to proximal defect of the dentary or of the middle and external ear whereas derivatives of the distal part of the first arch are not affected. Interestingly, Dlx5;Dlx6 are expressed at higher level distally (Figs.…”

Section: ;Dlx6mentioning

confidence: 99%

Spatio‐temporal dynamics of gene expression of the Edn1‐Dlx5/6 pathway during development of the lower jaw

Vieux-Rochas

Mantero

Heude

et al. 2010

Genesis

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Summary: The morphogenesis of the vertebrate skull results from highly dynamic integrated processes involving the exchange of signals between the ectoderm, the endoderm, and cephalic neural crest cells (CNCCs). Before migration CNCCs are not committed to form any specific skull element, molecular signals exchanged in restricted regions of tissue interaction are crucial in providing positional identity to the CNCCs mesenchyme and activate the specific morphogenetic process of different skeletal components of the head. In particular, the endothelin-1 (Edn1)-dependent activation of Dlx5 and Dlx6 in CNCCs that colonize the first pharyngeal arch (PA1) is necessary and sufficient to specify maxillo-mandibular identity. Here, to better analyze the spatio-temporal dynamics of this process, we associate quantitative gene expression analysis with detailed examination of skeletal phenotypes resulting from combined allelic reduction of Edn1, Dlx5, and Dlx6. We show that Edn1-dependent and -independent regulatory pathways act at different developmental times in distinct regions of PA1. The Edn1?Dlx5/6?Hand2 pathway is already active at E9.5 during early stages of CNCCs colonization. At later stages (E10.5) the scenario is more complex: we propose a model in which PA1 is subdivided into four adjacent territories in which distinct regulations are taking place. This new developmental model may provide a conceptual framework to interpret the craniofacial malformations present in several mouse mutants and in human first arch syndromes. More in general, our findings emphasize the importance of quantitative gene expression in the fine control of morphogenetic events. genesis 48:362-373, 2010.

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Mesenchymal patterning byHoxa2requires blocking Fgf-dependent activation ofPtx1

Cited by 39 publications

References 47 publications

IGFBP5 is a potential regulator of craniofacial skeletogenesis

IGFBP5 is a potential regulator of craniofacial skeletogenesis

Altered expressions of HOX genes in human cutaneous malignant melanoma

Spatio‐temporal dynamics of gene expression of the Edn1‐Dlx5/6 pathway during development of the lower jaw

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