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At least 1,009 records · Page 56Linked to original sources
PubMed2003

Pbx1 regulates nephrogenesis and ureteric branching in the developing kidney.

Pbx1 encodes a TALE homeodomain transcription factor that regulates developmental gene expression in a variety of tissues. Loss-of-function studies have demonstrated a critical role for Pbx1 in cellular proliferation and patterning and suggest its involvement in numerous regulatory pathways. In this study, examination of metanephric development in Pbx1(-/-) embryos was conducted to further elucidate Pbx1-dependent processes during organogenesis. Prior to death at E15.5, Pbx1(-/-) embryos displayed kidneys that were reduced in size, axially mispositioned, and in more severe cases, exhibited unilateral agenesis. Analysis with molecular markers revealed the effective induction of tubulogenic mesenchyme; however, Pbx1(-/-) kidneys contained fewer nephrons and were characterized by expanded regions of mesenchymal condensates in the nephrogenic zone. Despite the restricted expression of Pbx1 in metanephric mesenchyme, developing nephrons, and stroma, decreased branching and elongation of the ureter were also observed. Moreover, heterologous recombination studies with explant cultures verified that Pbx1(-/-) renal defects arose exclusively from mesenchymal dysfunction. Taken together, these data establish a role for Pbx1 in mesenchymal-epithelial signaling and demonstrate that Pbx1 is an essential regulator of mesenchymal function during renal morphogenesis.

Animals↗
PubMed1998

Developmental changes of gene expression in heme metabolic enzymes in rat placenta.

Transcription levels of the non-specific delta-aminolevulinate synthase (ALAS-N) and heme oxygenase-1 (HO-1) in the placenta at the terminal stage of pregnancy were comparable to those in the female adult liver and in the spleen, respectively. Immunohistochemical studies demonstrated that both enzymes were exclusively expressed in the trophoblast. During gestation, transcript of ALAS-N slightly increased, while HO-1 mRNA significantly decreased. Induced acute fetal hypoxia resulted in an increase in ALAS-N mRNA and in a decrease in HO-1 mRNA. These findings indicate that placental heme metabolism is influenced by the oxygen supply.

5-Aminolevulinate Synthetase↗
PubMed1998

Abnormal cholesterol biosynthesis as in Smith-Lemli-Opitz syndrome disrupts normal skeletal development in the rat.

Smith-Lemli-Opitz syndrome (SLOS) in human infants is a common autosomal recessive malformation syndrome (estimated incidence, 1:20,000). It is characterized clinically by congenital anomalies, especially craniofacial and limb defects, and biochemically by a defect in 7-dehydrocholesterol-delta7-reductase activity (7DHC-reductase), the final enzyme in cholesterol biosynthesis. In previous studies, early administration of the 7DHC-reductase inhibitor AY9944 to pregnant rats resulted in a high frequency of holoprosencephaly, relevant to craniofacial anomalies of SLOS. In order to test the effect of AY9944 on limb development, we treated dams on gestation day 7 (GD7), which delays the biochemical defect to about GD13 to GD14. Sera were sampled on GD12, GD14, and GD21 and cholesterol and dehydrocholesterols (7DHC and 8DHC) were measured by gas-chromatography-mass spectrometry (GC-MS), as for the diagnosis of SLOS. GD21 fetuses were examined for gross malformations and skeletal development. In treated dams, the SLOS biochemical marker 7DHC accounted for one fourth and one third of total sterols, respectively, on GD12 and GD14, and cholesterolemia on these two gestation days was reduced by 50% and 43%, respectively, as compared with control values. This maternal metabolic defect was associated with decrease in fetal weight and delayed ossification. In addition, scapular malformations were observed in four fetuses from three litters. The malformations could have been caused by the same mechanism as holoprosencephaly after early treatment with AY9944. These cholesterol-deficiency-based malformations could have a common cause in the abnormal expression of Hedgehog or other developmental gene proteins, and may thus explain various congenital polymalformative syndromes in humans, including SLOS.

Abnormalities, Drug-Induced↗
PubMed2002

Interchange of DNA-binding modes in the deformed and ultrabithorax homeodomains: a structural role for the N-terminal arm.

The deformed (Dfd) and ultrabithorax (Ubx) homeoproteins regulate developmental gene expression in Drosophila melanogaster by binding to specific DNA sequences within its genome. DNA binding is largely accomplished via a highly conserved helix-turn-helix DNA-binding domain that is known as a homeodomain (HD). Despite nearly identical DNA recognition helices and similar target DNA sequence preferences, the in vivo functions of the two proteins are quite different. We have previously revealed differences between the two HDs in their interactions with DNA. In an effort to define the individual roles of the HD N-terminal arm and recognition helix in sequence-specific binding, we have characterized the structural details of two Dfd/Ubx chimeric HDs in complex with both the Dfd and Ubx-optimal-binding site sequences. We utilized hydroxyl radical cleavage of DNA to assess the positioning of the proteins on the binding sites. The effects of missing nucleosides and purine methylation on HD binding were also analyzed. Our results show that both the Dfd and Ubx HDs have similar DNA-binding modes when in complex with the Ubx-optimal site. There are subtle but reproducible differences in these modes that are completely interchanged when the Dfd N-terminal arm is replaced with the corresponding region of the Ubx HD. In contrast, we showed previously that the Dfd-optimal site sequence elicits a very different binding mode for the Ubx HD, while the Dfd HD maintains a mode similar to that elicited by the Ubx-optimal site. Our current methylation interference studies suggest that this alternate binding mode involves interaction of the Ubx N-terminal arm with the minor groove on the opposite face of DNA relative to the major groove that is occupied by the recognition helix. As judged by hydroxyl radical footprinting and the missing nucleoside experiment, it appears that interaction of the Ubx recognition helix with the DNA major groove is reduced. Replacing the Dfd N-terminal arm with that of Ubx does not elicit a complete interchange of the DNA-binding mode. Although the position of the chimera relative to DNA, as judged by hydroxyl radical footprinting, is similar to that of the Dfd HD, the missing nucleoside and methylation interference patterns resemble those of the Ubx HD. Repositioning of amino acid side-chains without wholesale structural alteration in the polypeptide appears to occur as a function of N-terminal arm identity and DNA-binding site sequence. Complete interchange of binding modes was achieved only by replacement of the Dfd N-terminal arm and the recognition helix plus 13 carboxyl-terminal residues with the corresponding residues of Ubx. The position of the N-terminal arm in the DNA minor groove appears to differ in a manner that depends on the two base-pair differences between the Dfd and Ubx-optimal-binding sites. Thus, N-terminal arm position dictates the binding mode and the interaction of the recognition helix with nucleosides in the major groove.

Amino Acid Sequence↗
PubMed2003

Bilateral frontal polymicrogyria and epilepsy in a patient with Turner mosaicism: a case report.

Turner's syndrome (TS) is rarely associated with serious abnormalities of brain structure or malformations of cortical development. We report a 17-year-old girl with TS and 45,XO/46,XX mosaicism presenting bilateral frontal polymicrogyria (BFP) and epilepsy. To our knowledge, the association between TS and BFP has never been reported to date. Our observation confirms that in humans the X-chromosome plays an important role in the development and specialization of brain structure and function. We hypothesize that the absence or abnormalities of developmental genes localized on the X-chromosome could be involved in the pathogenesis of BFP observed in our patient.

Adolescent↗
PubMed1997

Embryonic neural chimeras in the study of vertebrate brain and head development.

Construction of neural chimeras between quail and chick embryos has been employed since 1969 when the unique nucleolar structure of the quail nucleus and its use to devise a cell marking technique by associating quail and chick cells in ovo were described in the "Bulletin Biologique de la France et de la Belgique." This method was first applied to the ontogeny of the neural crest, a structure whose development involves extensive cell migration, and, since 1984, to that of the central nervous system (CNS). This chapter highlights some of the most significant findings provided by this approach concerning the CNS, such as (i) demonstration of the common origin of the floor plate and notochord from a group of cells localized in the "organizer", i.e., Hensen's node, and the way in which these two structures become positioned respectively within and under the neural tube during gastrulation and neurulation in Amniotes; (ii) the neural crest origin of the skull vault and the facial and hypobranchial skeleton. This means that the mesodermal contribution to the skull is limited to the occipital and otic regions and extends only to the rostral limit of the notochord. A correlation can be drawn between the development of the telencephalon and the mesectodermally derived skull in the vertebrate phylum; (iii) demonstration that the midbrain-hindbrain junction, at the stage of the encephalic vesicles, acts as an organizing center for tectal and cerebellar structures. This function was correlated with the activity of several developmental genes, thus providing insight into their function during neurogenesis; (iv) the pattern of morphogenetic movements and cell migration taking place in defined brain-to-be areas, as well as the origin of various cell types of nervous tissues; and (v) a new avenue for studying brain localization of either behavioral traits or genetically encoded brain disorders.

Animals↗
PubMed2003

Fetal wound healing current perspectives.

Early in gestation, fetal wounds are capable of healing scarlessly. Scarless healing in the fetus is characterized by regeneration of an organized dermis with normal appendages and by a relative lack of inflammation. Although there is a transition period between scarless and scar-forming repair, scarless healing also depends on wound size and the organ involved. The ability to heal scarlessly, furthermore, appears to be intrinsic to fetal skin. Unique characteristics of fetal fibroblasts, inflammatory cells, extra-cellular matrix, cytokine profile, and developmental gene regulation may be responsible for the scarless phenotype of early gestation fetal wounds. With the current knowledge, only minimal success has been achieved with the topical application of neutralizing antibodies, antisense oligonucleotides, and growth factors to improve wound-healing outcomes. Thus, further investigation into the mechanisms underlying scarless repair is crucial in order to devise more effective therapies for scar reduction and the treatment of cirrhosis, scleroderma, and other diseases of excessive fibrosis.

Animals↗
PubMed1999

Visual-evoked potential evidence of chiasmal hypoplasia.

PURPOSE: To show that chiasmal hypoplasia or aplasia need not be an isolated developmental anomaly and to examine the spectrum of associated clinical findings to explore the possibility that these patients may represent a phenotypic manifestation of a developmental gene anomaly. DESIGN: An observational case series. PARTICIPANTS: Five infants, between several weeks and 7 months of age, in whom the electrophysiologic characteristic of chiasmal hypoplasia had been noted were included. METHODS: Flash electroretinography and flash and pattern visual-evoked potentials (VEPs) were elicited from all patients. Clinical ophthalmologic examinations, including funduscopy, were performed, and all patients had magnetic resonance imaging (MRI) brain scans. MAIN OUTCOME MEASURES: The occipital distribution of monocular VEP response peaks was studied. The symmetry of lateral channel responses was compared for monocular stimulation. RESULTS: All five patients had a crossed asymmetry in the monocular VEP occipital distribution, which is consistent with a paucity of fibers crossing at the chiasm. The MRI findings supported this electrophysiologic observation, illustrating degrees of chiasmal hypoplasia and variable coincidence of other midline abnormalities of the brain. Optic disc appearances varied from normal to hypoplastic and colobomatous. CONCLUSIONS: The ophthalmologic and MRI findings of five patients who showed a crossed asymmetry in monocular flash VEPs are consistent with a paucity of axons crossing at the chiasm. The similarities between achiasmia in humans and mice due to a Pax2 gene anomaly are discussed.

Coloboma↗
PubMed1999

Animal evolution. The end of the intermediate taxa?

Contrary to general belief, there has not been a reliable, global phylogeny of animals at hand within the past few decades. Recent progress in molecular phylogeny is rapidly changing the situation and has provided trees that constitute a reference frame for discussing the still controversial evolution of body plans. These trees, once purged of their possible artefacts, have already yielded confirmation of traditional, anatomically based, phylogenies as well as several new and quite significant results. Of these, one of the most striking is the disappearance of two superphyla (acoelomates such as flatworms, pseudocoelomates such as nematodes) previously thought to represent grades of intermediate complexity between diploblasts (organisms with two germ layers) and triploblasts (organisms with three germ layers). The overall image now emerging is of a fairly simple global tree of metazoans, comprising only a small number of major branches. The topology nicely accounts for the striking conservation of developmental genes in all bilaterians and suggests a new interpretation of the 'Cambrian explosion' of animal diversity.

Animal Population Groups↗
PubMed2006

[Congenital cataract: general review].

Cataract is a loss of lens transparency because of a protein alteration. Etiopathogenesis is poorly understood but new mutations of different developmental genes involved are found in 25% of cases. Frequency of onset, particularly when different ocular development anomalies occur, is related to the lens induction phenomena on the eye's anterior segment structure during embryologic development. Genetic transmission is often found on the dominant autosomal mode. Diagnosis is based on a complete and detailed examination of the eye, often with general anaesthesia. This condition predisposes children to later, sometimes serious amblyopia. Different clinical aspects can be observed: from cataract with ocular and/or systemic anomalies to polymalformative syndrome, skeletal, dermatological, neurological, metabolic, and genetic or chromosomal diseases. A general systematic pediatric examination is necessary. Congenital cataract requires first and foremost early diagnosis and a search for all etiologies. Surgical treatment is adapted case by case but it has progressed with the quality of today's intraocular lenses even if systematic implantation continues to be debated. Life-long monitoring is absolutely necessary.

Cataract↗
PubMedDate not supplied

Deuterostome brains: synopsis and commentary.

The living deuterostomes comprise six monophyletic groups: (1) echinoderms + hemichordates, (2) tunicates, (3) cephalochordates, (4) myxinoids, (5) petromyzontoids, and (6) gnathostomes. The morphotype of the craniote (myxinoids + petromyzontoids + gnathostomes) central nervous system (CNS) comprises a fixed number of histogenetic units, formed by the intersection of transversely oriented neuromeres and longitudinally arranged zones. A well-developed built-in, natural coordinate system adds the third dimension to this morphotype. The classical subdivisions of the craniote CNS: prosencephalon (P), mesencephalon (M), rhombencephalon (R), and spinal cord (S) are each composed of a number of neuromeres. Chordates (larval tunicates + cephalochordates + craniotes) share a highly characteristic axial complex, encompassing a dorsal tubular CNS, a notochord and bilateral series of segmental muscles. In all chordates the CNS can be divided into a rostral (P-like + M-like), an intermediate (R-like) and a caudal (S-like) sector, and sets of homologous developmental genes play a role in this tripartitioning. There are no indications for the presence of olfactory or other telencephalic regions in the brain of non-craniote chordates. Convincing evidence that parts of the chordate CNS are homologous to parts of the larval or adult CNS of non-chordate deuterostomes (echinoderms + hemichordates) is lacking. The dorsal tubular CNS is most probably a chordate autapomorphy.

Animals↗
PubMedDate not supplied

Analysis of Fgf15 expression pattern in the mouse neural tube.

The dynamic process of neural tube regionalization in vertebrates is regulated by the expression of developmental genes which appear in characteristic patterns at neuroepithelial transversal domains, which are called secondary organizers. The molecular code present in these neuroepithelial organizers controls the generation of morphogenetic signals that induce and maintain regional characteristics in the surrounding neuroepithelium. The product of the Fgf8 gene is a secreted protein that has been demonstrated to be the key molecule for the isthmic organizer and is also expressed in two other organizer regions: the zona limitans and the anterior neural ridge. Here we analyze the expression of Fgf15 at different stages of mouse development in relation to Fgf8 and Otx2 expression patterns.

Animals↗
PubMed1997

Characterization of csgA, a new member of the forespore-expressed sigmaG-regulon from Bacillus subtilis.

A new locus, csgA, has been identified in a search for developmental genes transcribed by E sigmaG in Bacillus subtilis. csgA has the potential to encode three small proteins, CsgAA, CsgAB and CsgAC. The latter two would be encoded by overlapping ORFs. csgA is expressed in the spore chamber of the differentiating cell and is under the control of sigmaG and the transcriptional regulatory protein SpoVT. Mutation of csgA did not affect spore formation but produced a subtle defect in the ability of the germinating spore to resume vegetative growth.

Amino Acid Sequence↗
PubMed1997

Congenital hypomyelinating neuropathy: a reversible case.

A boy was born at 39 weeks gestation with severe weakness and hypotonia, fractured femurs, poor suck and swallow, and absent deep tendon reflexes. Electrodiagnostic studies revealed marked slowing of motor nerve conduction velocities and normal muscle electrical activity with no evidence of acute denervation. Muscle biopsy showed mild type 2 fiber predominance, and sural nerve biopsy revealed large axons without myelin, and axons with insufficient amount of myelin for their diameter. There was no evidence of inflammation or demyelination. Gradual clinical improvement in tone and strength occurred in a cephalocaudal direction. By 4 months, motor nerve conduction velocities and clinical examination were normal apart from absent deep tendon reflexes. On review at 19 months, motor development and neurological examination were completely normal. Pathogenesis of this reversible pathologically documented case of congenital hypomyelinating neuropathy is unclear. No evidence was found for an inflammatory, toxic, metabolic, or demyelinating cause. Abnormal expression of a developmental gene, as in reversible cytochrome oxidase deficiency, may be a cause of this neuropathy.

Axons↗
PubMed1997

The XHex homeobox gene is expressed during development of the vascular endothelium: overexpression leads to an increase in vascular endothelial cell number.

The Hex/Prh homeobox gene is expressed in a subset of adult blood cell types and may play a role in the differentiation of the myeloid and B-cell lineages. In a search for homeobox genes involved in cardiovascular development, we have independently isolated a Xenopus laevis cDNA which appears to be the amphibian orthologue of Hex/Prh. Based on high sequence similarity in a number of regions, particularly the critical homeobox, we have named this gene XHex. This developmentally regulated gene is first expressed in the dorsal endomesoderm of the gastrula stage embryo. This tissue goes on to contribute to the structures of the embryonic liver and XHex continues to be expressed in the liver throughout development. From the tailbud stage, XHex is expressed in vascular endothelial cells throughout the developing vascular network. Vascular expression of XHex is transient and commences slightly after expression of the receptor tyrosine kinase gene, flk-1, which is known to be essential for vascular development. This observation raises the possibility that XHex is one of the transcription factors that responds to the VEGF/Flk-1 signal transduction pathway leading to differentiation of vascular endothelial cells. XHex is unique amongst homeobox genes in displaying expression in the endothelial layer throughout the developing vasculature. Overexpression of XHex sequences in the frog embryo causes disruption to developing vascular structures and an increase in the number of vascular endothelial cells, suggesting a possible role in regulation of cell proliferation.

Amino Acid Sequence↗
PubMed2000

Evolution of eyes.

Seeing is important for most species and it has been a key selective advantage throughout evolution. Consequently, there is a remarkable diversity among types of eyes. Animals have converged on eight optical solutions for collecting and focusing light; in contrast, all eyes share the same molecular strategy for absorbing photons. Recent studies have identified similarities in the genetic information that is used in the development of eyes, leading to the hypothesis that distinctly different eye types might have had a monophyletic origin. Across many species, there is a remarkable continuity of the developmental genes that participate in the construction of similar--but not necessarily homologous--eyes.

Animals↗
PubMed2001

Profiling brain transcription: neurons learn a lesson from yeast.

The application of microarray technologies to the brain poses unique challenges, because of the complexity of the central nervous system and the availability of resources. Nevertheless, recent studies using DNA chips have made inroads into the molecular characterization of regional and functional brain units, the identification of developmental gene expression patterns, and the discovery of transcriptional differences associated with behavioral and neuropathological traits.

Animals↗
PubMed1994

Comparative development. Seeing eye to eye.

Comparative studies of homologous developmental genes in mouse and Drosophila are suggesting that organs in these species may have closer evolutionary relationships than was hitherto suspected.

Animals↗