A5010040572- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Wnt/β-catenin signaling in development and cancer
- Neurogenesis and neuroplasticity mechanisms
- Craniofacial Disorders and Treatments
- Cancer-related gene regulation
- Pluripotent Stem Cells Research
- Hedgehog Signaling Pathway Studies
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- Retinoids in leukemia and cellular processes
- Cleft Lip and Palate Research
- RNA Research and Splicing
- Neurobiology and Insect Physiology Research
- MicroRNA in disease regulation
- Neonatal Respiratory Health Research
- Retinal Development and Disorders
- Congenital Ear and Nasal Anomalies
- Delphi Technique in Research
- Protease and Inhibitor Mechanisms
- Biomedical and Engineering Education
- Cancer-related molecular mechanisms research
- Axon Guidance and Neuronal Signaling
- Heart Failure Treatment and Management
New York University
2016-2025
University of Pennsylvania
2004-2013
National Institutes of Health
1994-2003
Eunice Kennedy Shriver National Institute of Child Health and Human Development
1994-2003
National Cancer Institute
1997
Corvallis Environmental Center
1997
Université Toulouse III - Paul Sabatier
1989-1995
Centre National de la Recherche Scientifique
1989-1995
École Normale Supérieure - PSL
1992-1994
Inserm
1990-1993
Members of the Wnt family signaling molecules are expressed differentially along dorsal–ventral axis developing neural tube. Thus we asked whether factors involved in patterning nervous system this axis. We show that Wnt-1 and Wnt-3a, both which dorsal portion tube, could synergize with inducers noggin chordin Xenopus animal explants to generate most structure, crest, as determined by expression Krox-20 , AP-2 slug . Overexpression or Wnt-3a neuroectoderm whole embryos led a dramatic...
The SOX family of transcription factors has been implicated in cell fate specification during embryogenesis. One member this family, Sox9, shown to regulate both chondrogenesis and sex determination the mouse embryo. Heterozygous mutations Sox9 result Campomelic Dysplasia (CD), a lethal human disorder characterized by autosomal XY reversal, severe skeletal malformations several craniofacial defects. is also expressed neural crest progenitors but very little known about function crest. We...
We report experiments with Xenopus laevis , using both intact embryos and ectodermal explants, showing that the transcription factor AP2α is positively regulated by bone morphogenetic protein (BMP) Wnt signaling, this activation an essential step in induction of neural crest (NC). Ectopic expression sufficient to activate high-level NC-specific genes such as Slug Sox9 which can occur isolated domains within plate well expansion endogenous NC territories. also has property inducing ectoderm...
In Xenopus, the neural plate border gives rise to at least three cell populations: crest, preplacodal ectoderm, and hatching gland. To understand molecular mechanisms that regulate formation of these lineages, we have analyzed role two transcription factors, Pax3 Zic1, which are among earliest genes activated in response border-inducing signals. At end gastrulation, Zic1 coexpressed crest forming region. addition, is expressed progenitors gland, detected ectoderm. Using gain function...
Abstract Craniofacial microsomia (CFM) is the second most common congenital facial anomaly, yet its genetic etiology remains unknown. We perform whole-exome or genome sequencing of 146 kindreds with sporadic (n = 138) familial 8) CFM, identifying a highly significant burden loss function variants in SF3B2 (P 3.8 × 10 −10 ), component U2 small nuclear ribonucleoprotein complex, probands. describe twenty individuals from seven harboring de novo transmitted haploinsufficient . Probands display...
Retinoic acid receptor (RAR) and retinoid X (RXR) form heterodimers regulate retinoid-mediated gene expression. We studied binding of RXR- RAR-selective ligands to the RXR-RAR heterodimer subsequent transcription. In limited proteolysis analyses, both RXR RAR in bound their respective underwent a conformational change presence retinoic acid-responsive element. reporter ligand (but not ligand), when added singly, activated transcription, but coaddition two led synergistic activation This...
Wnts are a large family of secreted molecules implicated in numerous developmental processes. Frizzled proteins likely receptors for and required Wnt signaling invertebrates. A number vertebrate frizzled genes have also been identified, but their roles mediating specific responses to endogenous not well defined. Using functional assay Xenopus, we performed screen identify potential interactions between frizzleds. We find that by Xwnt1, other Wnts, can be specifically enhanced 3 (Xfz3). As...
Among the families of transcription factors expressed at neural plate border, Sox proteins have been shown to regulate multiple aspects crest development. Sox8, Sox9 and Sox10, exhibit overlapping expression domains in progenitors, studies mouse suggest that Sox8 functions redundantly with Sox10 during Here, we show Xenopus, accumulates lateral edges mid-gastrula stage; contrast its chick orthologs, precedes progenitors. Later development, persists migrating cranial cells as they populate...
Two independent signals are necessary for neural crest (NC) induction in Xenopus: a Bmp signal, which must be partially attenuated by antagonists, and separate signal mediated either canonical Wnt or an Fgf. The mesoderm underlying the NC-forming region has been proposed as source of this second signal. Wnt8 Fgf8a expressed tissue around time NC therefore good candidate inducers. Loss-of-function studies indicate that both these ligands to specify NC; however, it is unclear whether signaling...
In vitro modeling is a powerful approach to investigate the pathomechanisms driving human congenital conditions. Here, we use embryonic stem cells (hESCs) model Nager and Rodriguez syndromes, two craniofacial conditions characterized by hypoplastic neural crest-derived bones, caused pathogenic variants of SF3B4, core component spliceosome. We observed that siRNA-mediated knockdown SF3B4 interferes with production hESC-derived crest cells, as seen marked reduction in gene expression. This...
Nager and Rodriguez syndromes are rare craniofacial limb disorders characterized by midface retrusion, micrognathia, absent thumbs radial hypoplasia. These result from haploinsufficiency of SF3B4 (splicing factor 3b, subunit 4), a component the pre-mRNA spliceosomal machinery. Although spliceosome is present functions in all cells body, most spliceosomopathies - including cell- or tissue-specific their pathology. To understand pathomechanism underlying these conditions, we generated Xenopus...
The Dmrt genes encode a large family of transcription factors whose function in sexual development has been well studied. However, their expression pattern is not restricted to the gonad, suggesting that might regulate other developmental processes. Here, we report and functional analysis one member this family: Xenopus Dmrt4 ( XDmrt4 ). initially expressed anterior neural ridge then becomes progressively part telencephalon olfactory placode/epithelium. induced at plate by balance inducers...