Antonio Baldini

..Furthermore, our data link, for the first time, the function of the secondary heart field to congenital heart disease...

..Tbx1 is an excellent tool to probe the genetic network governing embryonic pharyngeal development...

..We also thereby demonstrate conclusively that the role of Tbx1 in fourth PAA development is cell non-autonomous...

..Consistent with clinical data, experiments in mice indicate that genetics can only explain part of the phenotypic variability. The recent identification of phenotypic modifiers further underscores the complex genetics of this syndrome...

..These experiments have revealed substantially different sensitivity to gene dosage in different tissues and at different times, underlying the importance of the developmental context within which gene dosage reduction occurs...

..This article is an update on DiGeorge syndrome research focusing on the synergy of human and model systems genetics toward the understanding of conotruncal and aortic arch defects...

..Thus, the mesodermal transcription program is not only crucial for cardiovascular development, but is also key in the development and patterning of pharyngeal endoderm...

..Our findings reveal that Wnt signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium...

..These data demonstrate new functional mechanisms for Tbx1 in tooth morphogenesis and provide a molecular basis for craniofacial defects in DiGeorge syndrome patients...

..Loss of Tbx1 results into hypoplasia of heart regions derived from the second heart field, a population of cardiac progenitors cells (CPCs). Thus, we hypothesized that Tbx1 is an important player in the biology of CPCs...

..Overall, our data suggest that there are developmental process-specific gene dosage thresholds beyond which the phenotype worsens very rapidly with very small mRNA level reductions...

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..This model provides a striking demonstration of the essential role played by the periotic mesenchyme in the organogenesis of the cochlea...

..A genetic-based blueprint of crucial developmental times for organs and systems should be a valuable asset for our understanding of birth defect pathogenesis...

..In addition, Fgf15 and Tbx1 do not interact genetically, suggesting that Fgf15 operates through a pathway independent of Tbx1. These studies reveal a novel role of Fgf15 during development of the cardiac outflow tract...

..Our findings reveal a novel pathway for the development of the lymphatic vessel network...

..We speculate that the FGF8 locus might affect the penetrance of cardiovascular defects in individuals with chromosome 22q11 deletions involving TBX1...

..The latter function is likely related to the known role of the Endothelin-1 pathway in neural crest function...

..Finally, we show that Tbx1(Cre)-positive and Tbx1(Cre)-negative cell descendants occupy discrete domains in the outflow tract throughout development...

..Our data suggest that Tbx1 deletion in del22q11 patients may cause not only external and middle ear defects but also sensorineural and vestibular phenotypes observed in these patients...

..Conditional inactivation in mice and manipulation of Pitx2 expression in chick mandible cultures revealed an autonomous function in expansion and survival of branchial arch mesoderm...

..We speculate that this may be a general mechanism of T-box function and that Baf60a is a key component of the transcriptional control in cardiac progenitors...

..Our data suggest a coordinated pathway modulating Fgf8 ligand expression and tissue response to it in the SHF...

..Overall, our data suggest a regulatory architecture of the Tbx1 gene made of tissue-specific modules and redundant elements that individually contribute, to a modest extent, to the expression of the gene...

..Therefore, we have identified a new dosage-sensitive genomic region that may be critical for normal heart development in both mice and humans...

..The medical significance of these studies is not only relevant to congenital heart disease, but also to the biology of cardiac cell regeneration...

..Thus, by disrupting the endogenous TAK1 locus, we prove a pivotal role for TAK1 in the LKB1/AMPK signaling axis, an essential governor of cell metabolism...

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..We hypothesize that this is due to the lack of a guidance role from the pouch endoderm, which is missing in these mutants...

..However Crkl, another gene implicated in the 22q11DS phenotype, was found to be downregulated by microarray and RTQPCR...

..Overall, our data reveal specific and regionally restricted distribution of SERT-expressing cells in the developing heart of mouse...

..Finally, analysis of the Tbx1-mesoderm-specific knockout mouse demonstrated the cell autonomous requirement for Tbx1 during myocyte development in the cranial mesoderm...

..We conclude that the main functions of Tbx1 in the inner ear are to control, cell-autonomously, contribution, size and fate of a large population of otic epithelial cells, and, cell non-autonomously, cochlear morphogenesis...

..These experiments highlight which genes and pathways potentially affected by lack of Tbx1, and whose role may be explored further by testing for epistasis using mouse mutants...

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