A5009712815- Hedgehog Signaling Pathway Studies
- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Plant Molecular Biology Research
- Wnt/β-catenin signaling in development and cancer
- Genetic and rare skin diseases.
- Plant Gene Expression Analysis
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Healthcare Policy and Management
- Congenital Ear and Nasal Anomalies
- Global Health Workforce Issues
- Genetics and Neurodevelopmental Disorders
- Developmental Biology and Gene Regulation
- Healthcare Systems and Reforms
- Genetic and Kidney Cyst Diseases
- Cleft Lip and Palate Research
- Bone fractures and treatments
- Cancer Cells and Metastasis
- Connective tissue disorders research
- Bacterial Genetics and Biotechnology
- Biochemical Analysis and Sensing Techniques
- Microbial Metabolic Engineering and Bioproduction
- Plant Reproductive Biology
Stanford University
2010-2023
Howard Hughes Medical Institute
2001-2016
California Institute for Regenerative Medicine
2015
Institute for Stem Cell Biology and Regenerative Medicine
2012
Johns Hopkins University
2001-2004
University of California, Los Angeles
1991-1996
One of the most dominant influences in patterning multicellular embryos is exerted by Hedgehog (Hh) family secreted signaling proteins. Here, we identify a segment polarity gene Drosophila melanogaster, skinny hedgehog (ski), and show that its product required Hh-expressing cells for production appropriate activity imaginal precursors adult tissues. The ski encodes an apparent acyltransferase, provide genetic biochemical evidence Hh proteins from mutant retain carboxyl-terminal cholesterol...
Owing to their covalent modification by cholesterol and palmitate, Hedgehog (Hh) signaling proteins are localized predominantly the plasma membrane of expressing cells. Yet Hh also capable mobilizing eliciting direct responses from distant The zebrafish you gene, identified genetically >15 years ago, was more recently shown encode a secreted glycoprotein that acts cell-nonautonomously in pathway an unknown mechanism. We investigated function protein encoded murine Scube2, ortholog you, found...
Although the transporter-like protein Patched (Ptc) is genetically implicated in reception of extracellular Hedgehog (Hh) signal, a clear definition Hh receptor complicated by existence additional Hh-binding proteins and, Drosophila , lack physical evidence for direct binding to Ptc. Here we show that activity Ihog (Interference hedgehog), or its close relative Boi (Brother Ihog), absolutely required biological response and sequestration limit long-range signaling. We demonstrate interacts...
Cellular lipids are speculated to act as key intermediates in Hedgehog signal transduction, but their precise identity and function remain enigmatic. In an effort identify such lipids, we pursued a pathway inhibitory activity that is particularly abundant flagellar of Chlamydomonas reinhardtii, resulting the purification identification ergosterol endoperoxide, B-ring oxysterol. A mammalian analog ergosterol, 7-dehydrocholesterol (7-DHC), accumulates Smith-Lemli-Opitz syndrome, human genetic...
We have previously shown that nucleosome loss, obtained by repressing histone H4 mRNA synthesis, activates otherwise inactive PHO5, GAL1, and CYC1 gene promoters (fused to the bacterial beta-galactosidase [lacZ] reporter gene) moderate levels of activity (approximately 2 15% fully induced levels). now report loss expression two additional are normally independent mechanisms: CUP1 (induced heavy-metal toxicity) HIS3 amino acid starvation). Surprisingly, level CUP1-lacZ HIS3-lacZ activation...
How organs maintain and restore functional integrity during ordinary tissue turnover or following injury represents a central biological problem. The maintenance of taste sensory in the tongue was shown 140 years ago to depend on innervation from distant ganglion neurons, but underlying mechanism has remained unknown. Here, we show that Sonic hedgehog (Shh), which encodes secreted protein signal, is expressed these experimental ablation neuronal Shh expression causes loss receptor cells...
Binding of the Hedgehog (Hh) protein signal to its receptor, Patched, induces accumulation seven-pass transmembrane Smoothened (Smo) within primary cilium and zinc finger transcription factor Gli2 at ciliary tip, resulting ultimately in Gli-mediated changes nuclear gene expression. However, mechanism by which pathway activation is communicated from Smo not known. In an effort elucidate this mechanism, we identified Dlg5 (Discs large, homolog 5) a biochemical screen for proteins that...
Previous work has shown that N-terminal deletions of yeast histone H3 cause a 2- to 4-fold increase in the induction GAL1 and number other genes involved galactose metabolism. In contrast, at H4 N terminus 10- 20-fold decrease these same GAL genes. However, each PHO5 only 4-fold. To define gene regulatory elements through which termini activate or repress transcription, fusions were made between promoter attached beta-galactosidase reporter gene. We show here hyperactivation caused by...
We have previously shown that nucleosome loss, obtained by repressing histone H4 mRNA synthesis, activates otherwise inactive PHO5, GAL1, and CYC1 gene promoters (fused to the bacterial beta-galactosidase [lacZ] reporter gene) moderate levels of activity (approximately 2 15% fully induced levels). now report loss expression two additional are normally independent mechanisms: CUP1 (induced heavy-metal toxicity) HIS3 amino acid starvation). Surprisingly, level CUP1-lacZ HIS3-lacZ activation...
OVERVIEW Histones fold DNA and block initiation of transcription in vitro. Recent evidence suggests that they also regulate the living cell ( Saccharomyces cerevisiae ). We describe genetic studies yeast histones show nucleosome loss is not merely a result, but cause, vivo. This model which activator proteins must first stimulate displacement or change structure prior to full activation preinitiation complex. However, more than just general repressor initiation. Core contain basic, flexible...
Failure to properly form bone or integrate surgical implants can lead morbidity and additional interventions in a significant proportion of orthopedic surgeries. While the role skeletal stem cells (SSCs) formation repair is well-established, very little known about factors that regulate downstream Bone, Cartilage, Stromal, Progenitors (BCSPs). BCSPs, as transit amplifying progenitor cells, undergo multiple mitotic divisions expand pool lineage committed progenitors allowing preserve their...