Downregulation of Grem1 expression in the distal limb mesoderm is a necessary precondition for phalanx development.

Background: The phalanges are the final skeletal elements to form in the vertebrate limb and their identity is regulated by signaling at the phalanx forming region (PFR) located at the tip of the developing digit ray. Here, we seek to explore the relationship between PFR activity and phalanx morphogenesis, which define the most distal limb skeletal elements, and signals associated with termination of limb outgrowth.

Results: As Grem1 is extinguished in the distal chick limb mesoderm, the chondrogenesis marker Aggrecan is up-regulated in the metatarsals and phalanges.

Quantifying cell-generated mechanical forces within living embryonic tissues.

Cell-generated mechanical forces play a critical role during tissue morphogenesis and organ formation in the embryo. Little is known about how these forces shape embryonic organs, mainly because it has not been possible to measure cellular forces within developing three-dimensional (3D) tissues in vivo. We present a method to quantify cell-generated mechanical stresses exerted locally within living embryonic tissues, using fluorescent, cell-sized oil microdroplets with defined mechanical properties and coated with adhesion receptor ligands.

Filopodia: the cellular quills of hedgehog signaling?

Reporting in Nature, Sanders et al. (2013) implicate filopodial projections in Sonic hedgehog (Shh) patterning of the limb. Actin-based filopodia transport Shh from producing cells, while filopodia of responding cells bear Cdon and Boc: coreceptors in the Shh pathway.

Transcriptional repression of VEGF by ZNF24: mechanistic studies and vascular consequences in vivo.

VEGF is a key regulator of normal and pathologic angiogenesis. Although many trans-activating factors of VEGF have been described, the transcriptional repression of VEGF remains much less understood. We have previously reported the identification of a SCAN domain-containing C2H2 zinc finger protein, ZNF24, that represses the transcription of VEGF.

Novel zebrafish model reveals a critical role for MAPK in lymphangiogenesis.

Purpose: Lymphatic disorders are poorly understood with few animal models. We designed a novel assay to measure lymphatic development using transgenic zebrafish with fluorescently labeled endothelial cells. Two major branches of the vascular endothelial growth factor receptor (VEGFR) signaling pathway were examined: the MAPK and PI3K pathways.

Chemical approaches to angiogenesis in development and regeneration.

Research on blood vessel formation has provided a great deal of information regarding both normal and pathological forms of angiogenesis during development and in different disease states. Central to these studies is the role of the vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). VEGF stimulation promotes the division, survival, and migration of endothelial cells, and is necessary for the formation of blood and lymphatic vessels.

Unique SMAD1/5/8 activity at the phalanx-forming region determines digit identity.

The zone of polarizing activity is the primary signaling center controlling anterior-posterior patterning of the amniote limb bud. The autopodial interdigits (IDs) are secondary signaling centers proposed to determine digit identity by acting on the cells of the digital ray. Here, we focus on events accompanying digital fate determination and define a region of the digital ray that expresses Sox9 and Bmpr1b and is phosphorylated-SMAD1/5/8 (p-SMAD1/5/8) positive.

An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis.

Establishment of angiogenic circuits that orchestrate blood vessel development and remodeling requires an exquisite balance between the activities of pro- and antiangiogenic factors. However, the logic that permits complex signal integration by vascular endothelium is poorly understood. We demonstrate that a "neuropeptide," neurokinin-B (NK-B), reversibly inhibits endothelial cell vascular network assembly and opposes angiogenesis in the chicken chorioallantoic membrane.

Regulation of Gremlin expression in the posterior limb bud.

Proper outgrowth of the limb bud requires a positive feedback loop between Sonic hedgehog (Shh) in the zone of polarizing activity (ZPA) and Fgfs in the overlying apical ectodermal ridge. The Bmp antagonist Gremlin is expressed in a domain anterior to the ZPA and is thought to act as a signaling intermediate between Shh and Fgf. It is currently unclear whether Shh acts directly or indirectly to initiate and maintain Gremlin.

The development of archosaurian first-generation teeth in a chicken mutant.

Modern birds do not have teeth. Rather, they develop a specialized keratinized structure, called the rhamphotheca, that covers the mandible, maxillae, and premaxillae. Although recombination studies have shown that the avian epidermis can respond to tooth-inductive cues from mouse or lizard oral mesenchyme and participate in tooth formation, attempts to initiate tooth development de novo in birds have failed.

The chick oligozeugodactyly (ozd) mutant lacks sonic hedgehog function in the limb.

We have analyzed a new limb mutant in the chicken that we name oligozeugodactyly (ozd). The limbs of this mutant have a longitudinal postaxial defect, lacking the posterior element in the zeugopod (ulna/fibula) and all digits except digit 1 in the leg. Classical recombination experiments show that the limb mesoderm is the defective tissue layer in ozd limb buds.

Expression of E2F-4 gene in colorectal adenocarcinoma and corresponding covering mucosa: an immunohistochemistry, image analysis, and immunoblot study.

E2F-4 is a transcription factor involved in the transition of the cell from the resting state (G0/G1) to the proliferative stage (S). It has been associated with the p107 and p130 members of the Rb-family and it is responsible for many important growth suppressive functions. E2F-1, one member of the E2F family, has a similar structure to E2F-4; however, both have different mechanisms of action in regulating cell-cycle progression.