genesis
Discovery and characterization of gene promoters, enhancers and repressor binding elements is an important research area in neuroscience. Here, the suitability of embryonic stem cells and their neural derivatives as a model system for this research is investigated. Three neural transgenic constructs (from the Mnx1, Fabp7, and tuba1a genes) that have been validated in transgenic mice were inserted...
The doublecortin (Dcx) gene encodes a microtubule‐binding protein that was originally found in immature neurons. In this study, we used two mouse strains that express reporter genes (LacZ and enhanced green fluorescence protein, respectively) driven by the endogenous Dcx promoter. We found that Dcx was expressed in the mesenchymal cells in the mouse embryonic limb buds. A population of the mesenchymal...
Axin1 is a critical negative regulator of the canonical Wnt‐signaling pathway. It is a concentration‐limiting factor in the β‐catenin degradation complex. Axin1 null mutant mouse embryos died at embryonic day 9.5, precluding direct genetic analysis of the roles of Axin1 in many developmental and physiological processes using these mutant mice. In this study, we have generated mice carrying two directly...
Studies using Drosophila have contributed significantly to our understanding of regulatory mechanisms that control stem cell fate choice. The Drosophila blood cell progenitor or prohemocyte shares important characteristics with mammalian hematopoietic stem cells, including quiescence, niche dependence, and the capacity to form all three fly blood cell types. This report extends our understanding of...
HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene located on chromosome 17p13.3, a region frequently hypermethylated or deleted in human neoplasias. In mouse, Hic1 is essential for embryonic development and exerts an antitumor role in adult animals. Since Hic1‐deficient mice die perinatally, we generated a conditional Hic1 null allele by flanking the Hic1‐coding region by loxP sites. When...
Section through the intestine of a P3 (postnatal day 3) Afp::mCherry; Afp::GFP double transgenic mouse. Red and green fluorescent reporter‐expressing cells are located in the endoderm layer along villi, but excluded from the crypt stem cell zone. See the article by Viotti at al. in this issue.
Cre‐expressing mouse lines constitute an important asset to mammalian genetics, allowing the deletion of genes in a spatio‐temporal specific manner. Our study on Hox gene function in lung development has led us to use a lung endoderm‐specific deletion with the Sftpc‐cre mouse line expressing the Cre recombinase gene under the control of human surfactant protein C regulatory sequences. In control experiments,...
The Cullin 4A(Cul4A) gene is important in cell survival, development, growth, and cell cycle control and is amplified in breast and hepatocellular cancers. Recently, we reported that Cul4A plays an oncogenic role in the pathogenesis of mesothelioma. An important strategy for studying Cul4A in different tissues is targeted overexpression of this gene in vivo. Studies of Cul4A in mice have been restricted...
Live imaging of genetically encoded fluorescent protein reporters is increasingly being used to investigate details of the cellular behaviors that underlie the large‐scale tissue rearrangements that shape the embryo. However, the majority of mouse fluorescent reporter strains are based on the green fluorescent protein (GFP). Mouse reporter strains expressing fluorescent colors other than GFP are therefore...
Antisense oligonucleotides are commonly employed to study the roles of genes in development. Although morpholino phosphorodiamidate oligonucleotides (morpholinos) are widely used to block translation or splicing of target gene products' the usefulness of other modifications in mediating RNase‐H independent inhibition of gene activity in embryos has not been investigated. In this study, we investigated...
Primary cilia are microtubule‐based organelles that serve as hubs for the transduction of various developmental signaling pathways includingHedgehog, Wnt, FGF, and PDGF. Ciliary dysfunction contributes to a range of disorders, collectively known as the ciliopathies. Recently, interest has grown in these syndromes, particularly among craniofacial biologists, as many known and putative ciliopathies...
Wnt/β‐catenin signaling initiates taste papilla development in mouse embryos, however, its involvement in taste cell turnover in adult mice has not been explored. Here we used the BATGAL reporter mouse model, which carries an engineered allele in which the LacZ gene is expressed in the presence of activated β‐catenin, to determine the responsiveness of adult taste bud cells to canonical Wnt signaling...
The Sox family of transcriptional regulators has been implicated in the control of a broad array of developmental processes. One member of this family SOX9 was first identified as a candidate gene for campomelic dysplasia (CD), a human syndrome affecting skeletal, and testis development. In these patients most endochondral bones of the face fail to develop resulting in multiple defects such as micrognathia,...
The formation and invagination of the optic stalk coincides with the migration of cranial neural crest (CNC) cells, and a growing body of data reveals that the optic stalk and CNC cells communicate to lay the foundations for periocular and craniofacial development. Following migration, the interaction between the developing eye and surrounding periocular mesenchyme (POM) continues, leading to induction...
Proper craniofacial development begins during gastrulation and requires the coordinated integration of each germ layer tissue (ectoderm, mesoderm, and endoderm) and its derivatives in concert with the precise regulation of cell proliferation, migration, and differentiation. Neural crest cells, which are derived from ectoderm, are a migratory progenitor cell population that generates most of the cartilage,...
The cephalic neural crest (NC) cells delaminate from the neuroepithelium in large numbers and undergo collective cell migration under the influence of multiple factors including positive and negative taxis, cell–cell interactions mediating cell sorting, cell cooperation, and Contact‐Inhibition of Locomotion. The migration has to be tightly regulated to allow NC cells to reach precise locations in...
Zebrafish craniofacial, skeletal, and tooth development closely resembles that of higher vertebrates. Our goal is to identify viable adult zebrafish mutants that can be used as models for human mineralized craniofacial, dental, and skeletal system disorders. We used a large‐scale forward‐genetic chemical N‐ethyl‐nitroso‐urea mutagenesis screen to identify 17 early lethal homozygous recessive mutants...
Normal patterning and morphogenesis of the complex skeletal structures of the skull requires an exquisite, reciprocal cross‐talk between the embryonic cephalic epithelia and mesenchyme. The mesenchyme associated with the jaws and the optic and olfactory capsules is derived from a Hox‐negative cranial neural crest (CNC) population that acts much as an equivalence group in its interactions with specific...
The effect of the brain on the morphology of the face has long been recognized in both evolutionary biology and clinical medicine. In this work, we describe factors that are active between the development of the brain and face and how these might impact craniofacial variation. First, there is the physical influence of the brain, which contributes to overall growth and morphology of the face through...