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PubMedDate not supplied

Expression of Pax2 and patterning of the chick inner ear.

Early regionalized gene expression patterns within the otocyst appear to correlate with and contribute to development of mature otic structures. In the chick, the transcription factor Pax2 becomes restricted to the dorsal and entire medial side of the otocyst by stage 16/17. The dorsal region of the otocyst forms the endolymphatic duct and sac (ED/ES), and the cochlear duct is derived from the ventromedial region. In the mouse, however, Pax2 expression is reported only in the ventromedial and not the dorsal otocyst. In Pax2 null mice, the cochlea is missing or truncated, but vestibular structures differentiate normally. Here we demonstrate that in the chick, the emerging ED/ES express high levels of Pax2 even when the position of the emerging ED is altered with respect to its environment, either by 180 degrees otocyst rotations about the anterior/posterior axis or transplantation of the otocyst into the hindbrain cavity. However, the Pax2 expression pattern is plastic in the rest of the otic epithelium after 180 degrees rotation of the otocyst. Pax2 is upregulated on the medial side (formerly lateral), and downregulated on the lateral side (formerly medial and expressing Pax2) indicating that Pax2 expression is influenced by the environment. Although Pax2 is upregulated in the epithelium after 180 degrees rotations in the region that should form the cochlear duct, cochlear ducts are truncated or absent, and the ED/ES emerge in a new ventrolateral position. Ablation of the hindbrain at the placode or early otic pit stage alters the timing of regionalized Pax2 expression in the otocyst. The resulting otocysts and ears are generally smaller, vestibular structures are abnormal, ED/ES are missing but cochlear ducts are of normal length. The hindbrain and dorsal periotic mesenchyme provide unique trophic and patterning information to the dorsal otocyst. Our results demonstrate that the ED is the earliest structure patterned in the inner ear and that the hindbrain is important for its specification. We also show that, although normal Pax2 expression is required for cochlear duct development, it is downstream of ventral otocyst patterning events.

Animals↗

PubMed1991

Pulmonary blastomas.

Pulmonary blastoma is a rare lung tumor composed of immature mesenchyme and/or epithelium that morphologically mimics embryonal pulmonary structure. The prognosis of these tumors is poor, and the clinical course is not readily predicted from histologic appearance. In this report, the clinical, gross, microscopic, and immunopathologic features of 52 cases are described, and prognostically important correlates are determined. Twenty-eight patients were women, and 24 were men. There was a unimodal age peak in the fourth decade; only two patients were younger than 10 years old, and both had biphasic blastomas. Forty-one percent of patients were asymptomatic. Chest radiography typically showed a peripheral or midlung mass without predilection for any lobe. Microscopically, tumors could be divided into two classes: those composed solely of malignant glands of embryonal appearance (well-differentiated fetal adenocarcinomas [WDFA], 28 cases) and those with a biphasic appearance (24 cases). The malignant epithelium contained cytokeratin, carcinoembryonic antigen, milk fat globulin, and often chromogranin; vimentin, actin, and less frequently desmin and myoglobin were present in malignant stromal cells. More often WDFA was a smaller tumor (less than 5 cm) than biphasic tumors (P less than or equal to 0.001). It was more likely to be asymptomatic (P less than or equal to 0.001), and it was less likely to show pleural effusion by chest radiography (P less than or equal to 0.01) or giant or bizarre tumor cells (P less than or equal to 0.001) or frequent (greater than or equal to 30 mitoses/10 high-power fields) mitoses in the microscopic sections (P less than or equal to 0.01). Only 14% of patients with WDFA died of their tumor; 52% of patients with biphasic tumors died (mean follow-up, 97 months and 49 months, respectively). For patients with WDFA, the presence of thoracic adenopathy by chest radiography (P less than or equal to 0.001) and metastasis at initial presentation (P less than or equal to 0.001), followed by tumor recurrence (P less than or equal to 0.01), were the factors most highly correlated with poor prognosis. For patients with biphasic tumors, tumor recurrence (P less than or equal to 0.001) was the most significant indicator of poor prognosis, followed by metastasis at initial presentation (P less than or equal to 0.05) and gross size of the tumor (greater than or equal to 5 cm) (P less than or equal to 0.05). These findings support the idea that histologic class and gross and clinical findings can be of prognostic value in pulmonary blastoma.

Actuarial Analysis↗

PubMed1993

Pattern formation in the developing mammalian forebrain: selective adhesion of early but not late postmitotic cortical and striatal neurons within forebrain reaggregate cultures.

The mammalian cerebral cortex and striatum exhibit spatially restricted distributions of neurons. These neuronal collectives correlate with the age at which the neurons become postmitotic. We investigated in vitro the role of cell adhesion in the organization of like-birthdated neurons within the rat telencephalon. Specifically, the ability of neurons of similar birthdate to reassociate with one another within either striatal or cortical reaggregates was observed. Early postmitotic neurons (destined for the striatal patch compartment and cortical deep layers) or later born neurons (destined for the striatal matrix compartment and cortical superficial layers) were labeled in vivo with [3H]-thymidine or bromodeoxyuridine (Brdu) on Embryonic Day (E) 13 or 18, respectively. Two or seven days later, the striatum and cortex were separately removed, dissociated, and reaggregated in suspension cultures for 5 days. Within both striatal and cortical reaggregates, E13 [3H]thymidine-labeled cells were observed to clump together toward the center of the reaggregates. Conversely, reaggregates containing cells labeled on E18 with a single [3H]thymidine injection or with two separate Brdu injections contained labeled cells which were dispersed with respect to each other, but showed an overall distribution toward the periphery of the reaggregates. These results suggest that early, but not late, postmitotic striatal and cortical neurons selectively associate with one another within their respective structures. Dissociated embryonic striatal and cortical neurons were then co-reaggregated to examine if a single adhesive mechanism is shared by both tissues. Early born neurons within these reaggregates clustered with each other regardless of tissue type. Later born cortical and striatal neurons were found dispersed in relation to each other and the early born neurons. However, the selective adhesion of early born striatal and cortical neurons is not an attribute of all early postmitotic forebrain neurons, because dissociated early born septal-basal forebrain neurons were found dispersed within reaggregates of septal-basal forebrain tissue or when cocultured with striatal tissue. These results suggest that the organization of cortical and striatal neuronal groups may depend on a common adhesive mechanism that crosses tissue-type boundaries.

Animals↗

PubMed1995

Altered mitochondrial morphology of rat embryos in diabetic pregnancy.

BACKGROUND: Previous studies in vivo and in vitro have suggested that the oxidative metabolism of the embryo may have a role in the teratogenicity of diabetic pregnancy. In particular, the production of reactive oxygen species by the embryonic mitochondria has been implicated in the teratological process. The induction of congenital malformations by the diabetic milieu occurs during the early embryonic development. The present study aimed to estimate the role of the embryonic mitochondria in the teratological process of diabetic pregnancy by studying mitochondrial morphology in the embryos exposed to a diabetic environment in vivo or in vitro during early organogenesis and late fetal development. METHODS: For studies in vivo embryos of control or streptozotocin-diabetic rats were taken at gestational days 9-11 and subjected to light and electron microscopical analysis. The brain, heart, and liver of day-15 fetuses were also observed. For studies in vitro day-9 embryos of normal rats were cultured in a whole-embryo culture system for 48 hours. The culture media were supplied with high concentration of diabetes-related substrates and metabolites, and their effect on structure of embryonic neuroepithelial cells determined. RESULTS: The light microscopical observations demonstrated numerous cytoplasmic vacuoles in the ectoderm of day-9 embryos and in the neuroepithelium and blood cells of day-10 and day-11 embryos of diabetic rats. Ultrastructurally, these vacuoles were found to be mitochondria undergoing large-amplitude swelling with loss of matrix density and disturbed cristae. In contrast, no mitochondrial differences were found in the brain, heart, and liver, when day-15 fetuses from normal and diabetic rats were compared. Ultrastructural analysis of day-9 embryos cultured for 48 hours in the presence of high concentrations of D-glucose, pyruvate, beta-hydroxybutyrate, and alpha-ketoisocaproate also showed high-amplitude mitochondrial swelling in the neuroepithelium. The mitochondrial swelling was, however, not found in embryos cultured in a high concentration of L-glucose, excluding simple osmotic effects of the diabetes-related substrates and metabolites. CONCLUSIONS: The mitochondrial morphological changes appeared in embryos subjected to a diabetic environment during a time period when the congenital malformations in diabetic pregnancy are induced. The results support the notion that embryonic mitochondria are involved in the teratological process of diabetic pregnancy.

Animals↗

PubMed1992

Coincident loss of mitochondria and nuclei during lens fiber cell differentiation.

During normal differentiation, lens fiber cells lose their nuclei, mitochondria, and other membrane-bound organelles. In the present study, a slice preparation of the embryonic chicken lens was used with laser scanning confocal microscopy to study the spatial and temporal patterns of organelle breakdown during embryonic development. At all stages examined, mitochondria in lens epithelial cells were present in perinuclear clusters. In contrast, early in development, lens fiber cells contained extremely elongated mitochondria (> 100 microns) that were distributed throughout the cytoplasm and oriented along the long axis of the cells. By the 8th day of embryonic development (E8), the mitochondria in the central fiber cells began to fragment. At the same time, the nuclei in these cells became smaller and more spherical. By E10, mitochondrial staining in the central fibers became punctate. Electron microscopy of this region revealed swollen mitochondria with disrupted cristae. By E12, cells in the central region of the lens lacked mitochondria and nuclei. The loss of nuclei and mitochondria from a given cell was coincident and abrupt (2-4 hr), occurring in a previously unsuspected domain situated about 300 microns from the anterior surface of the lens. A cytoskeletal component, actin, persisted in the central cells indicating that organelle degradation represents a selective process and not simply the global degradation of supramolecular structures. Throughout embryonic development, the organelle-free region grew at approximately the same rate as the lens and, by the time of hatching, had expanded to match the diameter of the pupil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2001

Morphogenesis of prechordal plate and notochord requires intact Eph/ephrin B signaling.

Eph receptors and their ligands, the ephrins, mediate cell-to-cell signals implicated in the regulation of cell migration processes during development. We report the molecular cloning and tissue distribution of zebrafish transmembrane ephrins that represent all known members of the mammalian class B ephrin family. The degree of homology among predicted ephrin B sequences suggests that, similar to their mammalian counterparts, zebrafish B-ephrins can also bind promiscuously to several Eph receptors. The dynamic expression patterns for each zebrafish B-ephrin support the idea that these ligands are confined to interact with their receptors at the borders of their complementary expression domains. Zebrafish B-ephrins are expressed as early as 30% epiboly and during gastrula stages: in the germ ring, shield, prechordal plate, and notochord. Ectopic overexpression of dominant-negative soluble ephrin B constructs yields reproducible defects in the morphology of the notochord and prechordal plate by the end of gastrulation. Notably disruption of Eph/ephrin B signaling does not completely destroy structures examined, suggesting that cell fate specification is not altered. Thus abnormal morphogenesis of the prechordal plate and the notochord is likely a consequence of a cell movement defect. Our observations suggest Eph/ephrin B signaling plays an essential role in regulating cell movements during gastrulation.

Amino Acid Sequence↗

PubMed1977

Cleavage of pm7G from mRNA 5' terminal cap structures by pyrophosphatase activity in embryonic chick lens cells.

The presence of pyrophosphatase activity in embryonic lens cells which cleaves pm7G and ppGm from m7G(5')pppGm was demonstrated. It was also found that m7G(5')pppG, but not G(5')pppG, was hydrolyzed, and conversion of m7GpppG to m7G*pppG, in which the 5-membered ring of the m7G moiety is open, abolished its hydrolysis. For the caps hydrolyzed, pm7G was released only in the presence of lens cellular fraction; pm7G inhibited cap hydrolysis.

Animals↗

PubMed1979

Atrioventricular canal malformation interpreted as secondary to reduced compression upon the developing heart.

This study was undertaken to evaluate the nature and pathogenesis of malformations of the atrioventricular canal in relation to normal cardiogenesis. Serial histologic sections of normal human embryos and fetuses were made, from which three-dimensional images were reconstructed to show the relationship between the developing heart and its surrounding structures, and the course of development of the atrial septum and atrioventricular valves. Based on these reconstructions and on examination of the hearts of 59 patients with atrioventricular canal malformations, it is suggested that the spectrum of atrioventricular malformations may arise as a result of reduced compression of the developing atria by surrounding structures during embryonic Stages 13 through 18. Comparison of hearts with atrioventricular canal defects with normal embryos indicated that the malformations may be classified as primitive canals, complete canals, or partial canals, corresponding to failure of completion of normal development in Stages 14 through 18. In primitive canal the atrial septum was absent or had only a portion of septum primum. In complete canal both atrial septums were present, but the atrioventricular valve material was not subdivided and the four chambers were in communication. In partial canal, the atrioventricular valve was divided, but atrial and ventricular septal defects and valve clefts were present in varying degrees of severity. It is proposed that the spectrum of cardiac abnormalities which constitutes atrioventricular canal malformations may be understood as arising from varying degrees of lack of normal compression of the developing heart by surrounding structures. (Am J Pathol 95.579-598, 1979)

Adolescent↗

PubMed2007

Somatic cell nuclear transfer (SCNT) in mammals: the cytoplast and its reprogramming activities.

It is now more than nine years since Dolly, the world's first somatic cell cloned mammal was born, and the success of somatic cell nuclear transfer (SCNT) is still disappointingly low. Only about 3-5% of reconstructed embryos develop to term, and it is also evident that even if some clones are born, they are not necessarily fully developed and healthy. Embryonic and neonatal abnormalities of cloned offspring are probably a result of incorrect or incomplete reprogramming of the transferred donor cell nuclei. Such an incomplete reprogramming reflects the extremely low efficiency of SCNT. The key role in the process of reprogramming has been attributed to the enucleated oocyte-cytoplast into which the somatic cell nucleus is transferred. In our chapter, we will discuss the methodological approaches used for the preparation of cytoplasts and their possible reprogramming activities.

Animals↗

PubMed2000

Dynamic regulation of BDNF and NT-3 expression during visual system development.

Recent studies have proposed roles for neurotrophins in the formation and plasticity of ocular dominance columns as well as in the regulation of dendritic arborization in visual cortex of higher mammals. To assess potential roles for neurotrophins in these processes, we have examined the developmental expression of BDNF and NT-3 mRNA in the cat's visual system using in situ hybridization. BDNF and NT-3 mRNAs are dynamically regulated in many CNS structures during embryonic and postnatal development, and both mRNAs undergo striking developmental changes in laminar specificity and levels of expression within primary visual cortex during the critical period for ocular dominance column formation. Within visual cortex, BDNF mRNA is found in neurons in deep cortical layers (5 and 6) prior to eye opening, and in both deep and superficial layers (2 and 3) shortly afterwards. Within layer 4, the target of thalamocortical axons, BDNF mRNA is low initially and rises to high levels by the end of the critical period for ocular dominance column formation. NT-3 mRNA is first detectable in small stellate neurons at the base of layer 4 (4c) after eye opening, and levels decrease near the end of the critical period. BDNF and NT-3 mRNAs can be detected in the lateral geniculate nucleus at birth, and levels peak during the critical period. In both structures, BDNF mRNA expression is maintained into adulthood, while NT-3 is undetectable in the adult. The presence and dynamic regulation of these neurotrophins in visual structures is consistent with suggested roles for both of these neurotrophins in axonal and dendritic remodeling known to accompany the formation of ocular dominance columns.

Age Factors↗

PubMed2002

Pre-gut endoderm of chick embryos is regionalized by 1.5 days of development.

In this study, we set out to test the ability of endoderm from 1.5-day-old chick embryos (just before digestive tube formation) to develop region-specific characteristics when cultured heterotopically. Various parts of the 1.5-day endoderm were cultured in combination with the flank somatic mesoderm of 3- to 3.5-day chick embryos, and these cultures were analyzed for the expression of several transcription factors and the differentiation of the endoderm. By 1.5 days of normal development, the transcription factors, which are expressed in specific digestive organs, cSox2, CdxA, and cHoxb9/a13 were already expressed in the endodermal cells of the presumptive areas of their later expression domains. When 1.5-day pre-gut endoderm was cultured for 14-15 days, it showed specific differentiation into appropriate organ structures. In general, the more anterior part of the pre-gut endoderm formed the more rostral digestive organ structures while the posterior part became the caudal gut. The differentiation of these regions of endoderm matches their normal fate as recently elucidated (Matsushita [1996a] Rouxs Arch. Dev. Biol. 205:225-231; Matsushita [1999] Dev. Growth Differ. 41:313-319). Expression of cSox2, CdxA, and cHoxb9/a13 in endoderm cultured for 4-5 days is also consistent with their normal fate. Thus, each part of the pre-gut endoderm appears to be already regionally committed to some extent, in accordance with its fate by 1.5 days of development.

Animals↗

PubMed2003

The role of buttonhead and Sp1 in the development of the ventral imaginal discs of Drosophila.

The related genes buttonhead (btd) and Drosophila Sp1 (the Drosophila homologue of the human SP1 gene) encode zinc-finger transcription factors known to play a developmental role in the formation of the Drosophila head segments and the mechanosensory larval organs. We report a novel function of btd and Sp1: they induce the formation and are required for the growth of the ventral imaginal discs. They act as activators of the headcase (hdc) and Distal-less (Dll) genes, which allocate the cells of the disc primordia. The requirement for btd and Sp1 persists during the development of ventral discs: inactivation by RNA interference results in a strong reduction of the size of legs and antennae. Ectopic expression of btd in the dorsal imaginal discs (eyes, wings and halteres) results in the formation of the corresponding ventral structures (antennae and legs). However, these structures are not patterned by the morphogenetic signals present in the dorsal discs; the cells expressing btd generate their own signalling system, including the establishment of a sharp boundary of engrailed expression, and the local activation of the wingless and decapentaplegic genes. Thus, the Btd product has the capacity to induce the activity of the entire genetic network necessary for ventral imaginal discs development. We propose that this property is a reflection of the initial function of the btd/Sp1 genes that consists of establishing the fate of the ventral disc primordia and determining their pattern and growth.

Animals↗

PubMed1999

[Somite patterning and segregation of different somite lineages].

The somite is a transient embryonic mesodermal structure, found only in vertebrates. In amniotes, somites give rise to the dermis of the back, to the striated skeletal muscles of the trunk and limbs and to the vertebral column and ribs. Segregation of these different lineages is linked to the establishment of two somitic polarity axes, a dorso-ventral one and a medio-lateral one. While the establishment of the former relies essentially on extrinsic cues, that of the latter obeys to both intrinsic and extrinsic mechanisms. Concerning the environmental cues regulating the establishment of both axes, somitic regionalisation results from antagonistic or combinatorial influences mediated by diffusible factors, such as Sonic Hedgehog, Wnt and Bmp-4, that act in gradients.

Animals↗

PubMed2006

Separating the adhesive and signaling functions of the Fat and Dachsous protocadherins.

The protocadherins Fat (Ft) and Dachsous (Ds) are required for several processes in the development of Drosophila, including controlling growth of imaginal discs, planar cell polarity (PCP) and the proximodistal patterning of appendages. Ft and Ds bind in a preferentially heterophilic fashion, and Ds is expressed in distinct patterns along the axes of polarity. It has thus been suggested that Ft and Ds serve not as adhesion molecules, but as receptor and ligand in a poorly understood signaling pathway. To test this hypothesis, we performed a structure-function analysis of Ft and Ds, separating their adhesive and signaling functions. We found that the extracellular domain of Ft is not required for its activity in growth, PCP and proximodistal patterning. Thus, ligand binding is not necessary for Ft activity. By contrast, the extracellular domain of Ds is necessary and sufficient to mediate its effects on PCP, consistent with the model that Ds acts as a ligand during PCP. However, we also provide evidence that Ds can regulate growth independently of Ft, and that the intracellular domain of Ds can affect proximodistal patterning, both suggestive of functions independent of binding Ft. Finally, we show that ft mutants or a dominant-negative Ft construct can affect disc growth without changes in the expression of wingless and Wingless target genes.

Animals↗

PubMedDate not supplied

Expression of ARVCF in the human ganglionic eminence during fetal development.

ARVCF (armadillo repeat gene deleted in velocardiofacial syndrome) is a recently characterized member of the catenin p120 (ctn) subfamily of the armadillo repeat proteins. It is involved in modulation of cell-cell adhesion essential to many developmental processes including cellular rearrangement and migration. In the present study, by using specific immunohistochemical methods, strongly ARVCF-immunoreactive cells in a high packing density were found in the human ganglionic eminence (GE), a telencephalic structure which gives rise to precursor neurons of the striatum, the amygdala and the basal nucleus of Meynert. From 20 to 25 weeks of gestation, stripes of immunoreactive cells were found to extend from both the superior part of the GE towards the intermediate zone of the neocortex and from the inferior part of the GE either towards the amygdaloid complex or more laterally towards the intermediate zone. Bands of ARVCF-positive cells were also identified in the gangliothalamic body, a transient target for the migrating neurons from the GE to the thalamus. Double immunolabelling with ARVCF and calretinin antibodies, which mark the GE neurons migrating towards the cerebral cortex, revealed that a majority of ARVCF-positive neurons at the periphery of the GE and the cellular extensions from the GE also expressed calretinin. Our results implicate a very close association of ARVCF with migrating neurons from the GE.

Armadillo Domain Proteins↗

PubMed2001

Drosophila wing development in the absence of dorsal identity.

The developing wing disc of Drosophila is divided into distinct lineage-restricted compartments along both the anterior/posterior (A/P) and dorsal/ventral (D/V) axes. At compartment boundaries, morphogenic signals pattern the disc epithelium and direct appropriate outgrowth and differentiation of adult wing structures. The mechanisms by which affinity boundaries are established and maintained, however, are not completely understood. Compartment-specific adhesive differences and inter-compartment signaling have both been implicated in this process. The selector gene apterous (ap) is expressed in dorsal cells of the wing disc and is essential for D/V compartmentalization, wing margin formation, wing outgrowth and dorsal-specific wing structures. To better understand the mechanisms of Ap function and compartment formation, we have rescued aspects of the ap mutant phenotype with genes known to be downstream of Ap. We show that Fringe (Fng), a secreted protein involved in modulation of Notch signaling, is sufficient to rescue D/V compartmentalization, margin formation and wing outgrowth when appropriately expressed in an ap mutant background. When Fng and alphaPS1, a dorsally expressed integrin subunit, are co-expressed, a nearly normal-looking wing is generated. However, these wings are entirely of ventral identity. Our results demonstrate that a number of wing development features, including D/V compartmentalization and wing vein formation, can occur independently of dorsal identity and that inter-compartmental signaling, refined by Fng, plays the crucial role in maintaining the D/V affinity boundary. In addition, it is clear that key functions of the ap selector gene are mediated by only a small number of downstream effectors.

Animals↗

PubMed1985

Toxic effects of chemicals on mouse post-blastocyst development--a trial to establish a testing system for embryotoxicity.

We established a new testing system to assess embryotoxic chemicals using cultured preimplantation mouse embryos. Randomly bred Crj:CD-1 (ICR) mice were used. Late blastocysts collected on Day 4 of pregnancy (plug day:Day 1) were exposed for 24 hrs. to various chemicals at varying concentrations. Morphological embryonic development, structural chromosome aberrations and sister chromatid exchanges (SCEs) were examined as the parameters of embryotoxicity. Treated embryos were then transferred to pseudopregnant foster mice for the evaluation of in vivo development. Of the morphological developmental endpoints in vitro, the formation of two-layer ICMs (inner cell masses) was the most sensitive to the toxicity of chemicals, followed by ICMs and trophoblast outgrowth. Threshold limit values were confirmed regarding morphological growth. However, exposure of embryos to lower concentrations than threshold enhanced the frequency of chromosome aberrations and SCEs. Transfer of embryos treated with the lower concentration of 4-nitroquinoline 1-oxide induced not only fetal wastage but also developmental retardation. 4-nitroquinoline 1-oxide was the most embryotoxic in mouse blastocysts, followed in order by mitomycin C, bleomycin, methylmercuric chloride, diethylstilbestrol, mercuric chloride and ochratoxin-A. This new testing system appears to be a sensitive method of measuring the direct effects of toxic chemicals which yields results in a short term.

4-Nitroquinoline-1-oxide↗

PubMed2000

Role of angiopoietins in reproductive tract angiogenesis.

UNLABELLED: Components of the female reproductive system undergo a number of programmed angiogenic processes coupled with cyclic evolution and decline of ovarian, endometrial, and placental structures. The development of a new vascular network requires a remarkable degree of coordination between different cell types undergoing complex changes. This implies that the expression of the inciting angiogenic factors are hormone dependent. Recently, a second family of vascular endothelial growth factors was identified, the angiopoietins. Angiopoietins are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis, after the induction of new capillaries by vascular endothelial growth factor (VEGF). There are four known angiopoietins, and their specificity for the vascular endothelium results from the restricted expression pattern of their tyrosine kinase receptor, Tie2. In this review, we discuss the molecular characterization and mechanism of action of angiopoietin-1 and angiopoietin-2 in reproductive tract angiogenesis. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the angiogenic process and specifically explain the role of angiopoietics in reproductive tract angiogenesis and compare the differences between the various proteins that are involved in angiogenesis.

Angiopoietin-1↗