A5020493394- Hedgehog Signaling Pathway Studies
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Hearing, Cochlea, Tinnitus, Genetics
- Wnt/β-catenin signaling in development and cancer
- Congenital Ear and Nasal Anomalies
- Congenital heart defects research
- Hearing Loss and Rehabilitation
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Craniofacial Disorders and Treatments
- Congenital limb and hand anomalies
- Chromosomal and Genetic Variations
- Neurogenesis and neuroplasticity mechanisms
- Cleft Lip and Palate Research
- Genetics and Neurodevelopmental Disorders
- Kruppel-like factors research
- Congenital Heart Disease Studies
- Ear Surgery and Otitis Media
- Immune cells in cancer
- Bat Biology and Ecology Studies
- Prenatal Screening and Diagnostics
- Renal and related cancers
- Hippo pathway signaling and YAP/TAZ
University of Pennsylvania
2015-2024
Mount Sinai Hospital
2008
National Institute on Deafness and Other Communication Disorders
2002
University of Buenos Aires
2002
Harvard University
1993-1999
Howard Hughes Medical Institute
1995-1999
NYU Langone Health
1998
Brigham and Women's Hospital
1995
Cancer Research Center
1995
McGill University
1990-1994
ABSTRACT Induction of the floor plate at ventral midline neural tube is one earliest events in establishment dorsoventral (d/v) polarity vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog, has been shown to be both necessary and sufficient for this induction. In vertebrates, several downstream components signalling pathway have identified, including members Gli transcription factor family. study, we examined d/v patterning CNS Gli2 mouse mutants. We found that...
The anterior heart field (AHF), which contributes to the outflow tract and right ventricle of heart, is defined in part by expression LIM homeobox transcription factor Isl-1. importance Isl-1-positive cells cardiac development homeostasis underscored finding that these are required for act as stem/progenitor within postnatal heart. However, molecular pathways regulating cells' expansion differentiation poorly understood. We show AHF progenitor mice were responsive Wnt/beta-catenin signaling,...
The inner ear is partitioned along its dorsal/ventral axis into vestibular and auditory organs, respectively. Gene expression studies suggest that this subdivision occurs within the otic vesicle, tissue from which all structures are derived. While specification of ventral fates dependent on Shh secreted notochord, nature signal responsible for dorsal development has not been described. In study, we demonstrate Wnt signaling active in regions where it functions to regulate genes ( Dlx5/6 Gbx2...
Organization of the inner ear into auditory and vestibular components is dependent on localized patterns gene expression within otic vesicle. Surrounding tissues are known to influence compartmentalization vesicle, yet participating signals remain unclear. This study identifies Sonic hedgehog (Shh) secreted by notochord and/or floor plate as a primary regulator cell fates mouse ear. Whereas induction proceeds normally in Shh −/− embryos, morphogenesis greatly perturbed midgestation. Ventral...
The secreted protein sonic hedgehog (Shh) plays an integral role in forming the ventral midline of vertebrate central nervous system (CNS). In absence Shh function, development is perturbed resulting holoprosencephaly (HPE), a structural malformation brain, as well neuronal patterning and path finding defects along length anteroposterior neuraxis. Central to understanding neural tube how transcription regulated CNS. To address this issue, we devised enhancer trap assay systematically screen...
Sonic hedgehog (Shh) is a secreted signaling molecule for tissue patterning and stem cell specification in vertebrate embryos. Shh mediates both long-range short-range responses embryonic tissues through the activation repression of target genes by its Gli transcription factor effectors. Despite well-established functions development human disease, developmental regulation are virtually unknown. In this study, we investigate role control Myf5 , skeletal muscle regulatory gene cells previous...
Canonical Wnt signaling instructively promotes sensory neurogenesis in early neural crest stem cells (eNCSCs) (Lee, H.Y., M. Kleber, L. Hari, V. Brault, U. Suter, M.M. Taketo, R. Kemler, and Sommer. 2004. Science. 303:1020-1023). However, during normal development induces a fate only subpopulation of eNCSCs while other maintain their cell features, despite the presence activity. Hence, factors counteracting must exist. Here, we show that bone morphogenic protein (BMP) antagonizes...
Neural tube defects (NTDs) are very frequent congenital abnormalities in humans. Recently, we have documented independent association of Vangl1 and Vangl2 gene mutations with NTDs. In the Looptail mouse, homozygosity (but not heterozygosity) for loss-of-function alleles at causes severe NTD craniorachischisis, whereas heterozygosity mutant variants VANGL1 is associated NTDs a human cohort sporadic familial cases. To understand role normal development, created mouse an inactivating mutation...
Abstract The anterior pituitary gland drives highly conserved physiologic processes in mammalian species. These hormonally controlled are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current cellular models of anteiror pituitary, largely built on candidate gene based immuno-histochemical mRNA analyses, suggest that each the seven hormones synthesized by is produced a specific exclusive cell lineage. However, emerging evidence suggests more complex...
ABSTRACT Hedgehog (Hh) signaling plays a significant role in defining the polarity of variety tissue types along anterior/posterior and dorsal/ventral axes both vertebrate invertebrate organisms. The pathway through which Hh transduces its signal is still obscure, however, recent data have implicated cyclic AMP-dependent protein kinase A as negative regulator transduction pathway. One family members, Sonic hedgehog (Shh), can induce ventral neural cell vivo vitro; high concentrations floor...
ABSTRACT The axial midline mesoderm and the ventral of neural tube, floor plate, share property being a source secreted protein, Sonic hedgehog (Shh), which has capacity to induce variety cell types along length mouse CNS. To gain insight into mechanisms by Shh transcription is initiated in these tissues, we set out identify cis-acting sequences regulating gene expression. As an approach, have tested genomic clones encompassing 35 kb locus for their ability direct lacZ reporter temporally...
Organization of the vertebrate inner ear is mainly dependent on localized signals from surrounding tissues. Previous studies demonstrated that sonic hedgehog (Shh) secreted floor plate and notochord required for specification ventral (auditory) dorsal (vestibular) structures, yet it was not clear how this signaling activity propagated. To elucidate molecular mechanisms by which Shh regulates development, we examined embryos with various combinations mutant alleles Shh, Gli2 Gli3. Our study...
The establishment of the floor plate at ventral midline CNS is dependent on an inductive signaling process mediated by secreted protein Sonic hedgehog (Shh). To understand molecularly how induction proceeds we identified a Shh-responsive regulatory element that directs transgene reporter expression to and notochord in Shh-like manner characterized critical cis-acting sequences regulating this element. Cross-species comparisons narrowed activity Shh enhancer 88-bp sequence within intron 2...