Partial rescue of the Tbx1 mutant heart phenotype by Fgf8: Genetic evidence of impaired tissue response to Fgf8

Vitelli, Francesca; Lania, Gabriella; Huynh, Tuong; Baldini, Antonio

doi:10.1016/j.yjmcc.2010.08.023

Cited by 24 publications

(18 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These types of cardiovascular defects are characteristic of DiGeorge and Alagille syndromes and Fgf8 expression is reduced in mouse models of these syndromes, confirming the importance of maintaining appropriate levels of FGF signaling to prevent developmental anomalies (High et al 2009;Vitelli et al 2010).…”

Section: Signaling In Cell Differentiation and Morphogenesismentioning

confidence: 82%

Signaling in Cell Differentiation and Morphogenesis

Basson¹

2012

Cold Spring Harbor Perspectives in Biology

147

View full text Add to dashboard Cite

SUMMARYAll the information to make a complete, fully functional living organism is encoded within the genome of the fertilized oocyte. How is this genetic code translated into the vast array of cellular behaviors that unfold during the course of embryonic development, as the zygote slowly morphs into a new organism? Studies over the last 30 years or so have shown that many of these cellular processes are driven by secreted or membrane-bound signaling molecules. Elucidating how the genetic code is translated into instructions or signals during embryogenesis, how signals are generated at the correct time and place and at the appropriate level, and finally, how these instructions are interpreted and put into action, are some of the central questions of developmental biology. Our understanding of the causes of congenital malformations and disease has improved substantially with the rapid advances in our knowledge of signaling pathways and their regulation during development. In this article, I review some of the signaling pathways that play essential roles during embryonic development. These examples show some of the mechanisms used by cells to receive and interpret developmental signals. I also discuss how signaling pathways downstream from these signals are regulated and how they induce specific cellular responses that ultimately affect cell fate and morphogenesis.

show abstract

Section: Signaling In Cell Differentiation and Morphogenesismentioning

confidence: 82%

Signaling in Cell Differentiation and Morphogenesis

Basson¹

2012

Cold Spring Harbor Perspectives in Biology

147

View full text Add to dashboard Cite

show abstract

“…Previous studies have provided compelling evidence that Tbx1 functions upstream of a number of FGF genes (Vitelli et al, , ; Brown et al, ; Aggarwal et al, ; Arnold et al, ). In particular, the observation that Fgf8 expression is lost in the pharyngeal endoderm of Tbx1−/− embryos, taken together with the demonstration that Tbx1 and Fgf8 null alleles interact during pharyngeal development, provided strong evidence for a functional link between Tbx1 and the FGF signaling pathway (Vitelli et al, ).…”

Section: Discussionmentioning

confidence: 99%

Endoderm‐specific deletion of Tbx1 reveals an FGF‐independent role for Tbx1 in pharyngeal apparatus morphogenesis

Jackson

Kasah

Mansour

et al. 2014

Developmental Dynamics

View full text Add to dashboard Cite

Background The T-box transcription factor Tbx1, is essential for the normal development of multiple organ systems in the embryo. One of the most striking phenotypes in Tbx1−/− embryos is the failure of the caudal pharyngeal pouches to evaginate from the foregut endoderm. Despite considerable interest in the role of Tbx1 in development, the mechanisms whereby Tbx1 controls caudal pouch formation have remained elusive. In particular, the question as to how Tbx1 expression in the pharyngeal endoderm regulates pharyngeal pouch morphogenesis in the mouse embryo is not known. Results To address this question, we produced mouse embryos in which Tbx1 was specifically deleted from the pharyngeal endoderm and as expected, embryos failed to form caudal pharyngeal pouches. To determine the molecular mechanism, we examined expression of Fgf3 and Fgf8 ligands and downstream effectors. Although Fgf8 expression is greatly reduced in Tbx1-deficient endoderm, FGF signaling levels are unaffected. Furthermore, pouch morphogenesis is only partially perturbed by the loss of both Fgf3 and Fgf8 from the endoderm, indicating that neither are required for pouch formation. Conclusions Tbx1 deletion from the pharyngeal endoderm is sufficient to cause caudal pharyngeal arch segmentation defects by FGF-independent effectors that remain to be identified.

show abstract

“…ERK1/2 phosphorylation is reduced in mice with reduced or eliminated FGF8 expression and these animals have craniofacial and cardiovascular defects similar to those noted in Tbx1 - and Crkl -mutant mice, respectively (Abu-Issa et al, 2002; Park et al, 2006). In the second heart field Tbx1 is required for Fgf8 expression, and activation of ERK1/2 is significantly reduced in Tbx1 −/− cells (Vitelli et al, 2010). Shp2 is important for the normal development of cardiac neural crest cells.…”

Section: Cardiac Congenital Abnormalities Involving the Neural Crest mentioning

confidence: 99%

The neural crest in cardiac congenital anomalies

2012

View full text Add to dashboard Cite

This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions.

show abstract

Partial rescue of the Tbx1 mutant heart phenotype by Fgf8: Genetic evidence of impaired tissue response to Fgf8

Cited by 24 publications

References 17 publications

Signaling in Cell Differentiation and Morphogenesis

Signaling in Cell Differentiation and Morphogenesis

Endoderm‐specific deletion of Tbx1 reveals an FGF‐independent role for Tbx1 in pharyngeal apparatus morphogenesis

The neural crest in cardiac congenital anomalies

Contact Info

Product

Resources

About