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Antagonizing cAMP-dependent protein kinase A in the dorsal CNS activates a conserved Sonic hedgehog signaling pathway.

Hedgehog (Hh) signaling plays a significant role in defining the polarity of a variety of tissue types along the anterior/posterior and dorsal/ventral axes in both vertebrate and invertebrate organisms. The pathway through which Hh transduces its signal is still obscure, however, recent data have implicated the cyclic AMP-dependent protein kinase A as a negative regulator of the Hh signal transduction pathway. One of the vertebrate Hh family members, Sonic hedgehog (Shh), can induce ventral neural cell types both in vivo and in vitro; high concentrations induce floor plate and lower concentrat

Control of segmental asymmetry in Drosophila embryos.

During Drosophila development, an important aspect of body patterning is the division of the embryo into repeating morphological units referred to as parasegments. The parasegmental domains are first defined at the blastoderm stage by alternating stripes of transcripts encoded by the pair-rule genes fushi tarazu (ftz) and even-skipped (eve) and later by stripes encoded by the segment polarity genes engrailed (en) and wingless. Here, we show that the runt gene (run) is required to generate asymmetries within these parasegmental domains. Using a heat-shock-inducible run transgene, we found that

Expression of growth factors and growth factor receptors in human cleft-affected tissue.

OBJECTIVE. To investigate cleft disordered tissue in children with cleft palate and cleft lip with or without alveolar clefting for detection of local tissue growth factors and growth factor receptors and compare findings. Design. Morphological analysis of human tissue. Patients. Three groups were studied: 14 patients with cleft palate at the age from eight months to 18 years and two months, 12 patients with cleft lip with or without alveolar clefting in the age from four months to 15 years and four months and 11 control patients. RESULTS. In general, cleft palate disordered tissue showed more

Crosstalk between the EGFR and LIN-12/Notch pathways in C. elegans vulval development.

The Caenorhabditis elegans vulva is an important paradigm for cell-cell interactions in animal development. The fates of six vulval precursor cells are patterned through the action of the epidermal growth factor receptor-mitogen-activated protein kinase (EGFR-MAPK) inductive signaling pathway, which specifies the 1 degrees fate, and the LIN-12/Notch lateral signaling pathway, which specifies the 2 degrees fate. Here, we provide evidence that the inductive signal is spatially graded and initially activates the EGFR-MAPK pathway in the prospective 2 degrees cells. Subsequently, this effect is co

Conserved interactions with cytoskeletal but not signaling elements are an essential aspect of Drosophila WASp function.

Wiskott-Aldrich Syndrome proteins (WASp) serve as important regulators of cytoskeletal organization and function. These modular proteins, which are well-conserved among eukaryotic species, act to promote actin filament assembly in response to cues from various signal transduction pathways. Genetic analysis has revealed a requirement for the single Drosophila homolog, Wasp (Wsp), in cell-fate decisions governing specific neuronal lineages. We have used this unique developmental context to assess the contributions of established signaling and cytoskeletal partners of WASp. We present biochemical

The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice.

In the developing vertebrate CNS, members of the Wnt gene family are characteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon. In situ hybridization experiments demonstrate that one of the isolated Wnt genes, Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the

Is There a Unified Etiology of Hypoplastic Left Heart Syndrome? Evaluating Genetic, Structural, and Hemodynamic Models of Disease Initiation.

Background: Hypoplastic left heart syndrome (HLHS) is defined as "a spectrum of congenital cardiovascular malformations with normally aligne … al models and in utero interventions that demonstrate the impact of altered hemodynamics on cardiac morphogenesis. However, the flow theory fails to identify initial causes of disturbed flow or related histological features of HLHS like endocardial fibroelastosis. The myocardial and valve-first models suggest an important role in developmental defects, but do n …

Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality.

Mice lacking the epidermal growth factor receptor family member ErbB4 exhibit defects in cranial neural crest cell migration but die by embryonic day 11 because of defective heart development. To examine later phenotypes, we rescued the heart defects in ErbB4 mutant mice by expressing ErbB4 under a cardiac-specific myosin promoter. Rescued ErbB4 mutant mice reach adulthood and are fertile. However, during pregnancy, mammary lobuloalveoli fail to differentiate correctly and lactation is defective. Rescued mice also display aberrant cranial nerve architecture and increased numbers of large inter

Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system.

The novel homeobox-containing gene Vax1, a member of the Emx/Not gene family, is specifically expressed in the developing basal forebrain and optic nerve. Here, we show that Vax1 is essential for normal development of these structures. Mice carrying a targeted mutation of Vax1 show dysgenesis of the optic nerve, coloboma, defects in the basal telencephalon, and lobar holoprosencephaly. With the help of molecular markers we determined that in the developing visual system, the absence of Vax1 results in a proximal expansion of the activity of Pax6 and Rx. This observation suggests that Vax1 may

Wnt signaling induces epithelial differentiation during cutaneous wound healing.

BACKGROUND: Cutaneous wound repair in adult mammals does not regenerate the original epithelial architecture and results in altered skin function. We propose that lack of regeneration may be due to the absence of appropriate molecular signals to promote regeneration. In this study, we investigated the regulation of Wnt signaling during cutaneous wound healing and the consequence of activating either the beta-catenin-dependent or beta-catenin-independent Wnt signaling on epidermal architecture during wound repair. RESULTS: We determined that the expression of Wnt ligands that typically signal

BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium.

The neural crest is a multipotent, migratory cell population arising from the border of the neural and surface ectoderm. In mouse, the initial migratory neural crest cells occur at the five-somite stage. Bone morphogenetic proteins (BMPs), particularly BMP2 and BMP4, have been implicated as regulators of neural crest cell induction, maintenance, migration, differentiation and survival. Mouse has three known BMP2/4 type I receptors, of which Bmpr1a is expressed in the neural tube sufficiently early to be involved in neural crest development from the outset; however, earlier roles in other domai

A role of the cryptic gene in the correct establishment of the left-right axis.

During vertebrate embryogenesis, a left-right axis is established. The heart, associated vessels and inner organs adopt asymmetric spatial arrangements and morphologies. Secreted growth factors of the TGF-beta family, including nodal, lefty-1 and lefty-2, play crucial roles in establishing left-right asymmetries [1] [2] [3]. In zebrafish, nodal signalling requires the presence of one-eyed pinhead (oep), a member of the EGF-CFC family of membrane-associated proteins [4]. We have generated a mutant allele of cryptic, a mouse EGF-CFC gene [5]. Homozygous cryptic mutants developed to birth, but th

Pax3 and Pax7 are expressed in commissural neurons and restrict ventral neuronal identity in the spinal cord.

Pax3 and Pax7 are transcription factors sharing high sequence identity and overlapping patterns of expression in particular in the dorsal spinal cord. Analysis of Pax3 and Pax7 double mutant mice demonstrates that both genes share redundant functions to restrict ventral neuronal identity in the spinal cord. In their absence, the En1 expression domain is expanded dorsally but that of Evx1 is not affected. In addition, Pax3 and Pax7 are expressed in commissural neurons and double mutant embryos exhibit highly reduced ventral commissure. Our findings reveal two distinct regulatory pathways for sp

FGF-1 and FGF-7 induce distinct patterns of growth and differentiation in embryonic lung epithelium.

Fibroblast growth factors (FGFs) and receptors (FGFRs) are expressed in the developing lung and appear to be major regulators of lung growth and differentiation. By using mesenchyme-free lung epithelial cultures we show that FGF-1 (aFGF) and FGF-7 (KGF) produce different effects in the developing lung. FGF-1 stimulates epithelial proliferation that results in bud formation (branching), while FGF-7 promotes epithelial proliferation that leads to formation of cyst-like structures. In addition, FGF-7 stimulates epithelial differentiation, stimulating expression of SP-A and SP-B mRNA throughout th

Ft1, a novel gene related to ubiquitin-conjugating enzymes, is deleted in the Fused toes mouse mutation.

The dominant mouse mutation Fused toes is characterized by partial syndactyly of the limbs and thymic hyperplasia. Both morphological abnormalities were shown to be related to impaired regulation of programmed cell death. Ft/Ft embryos die in midgestation showing severe malformations of fore- and midbrain as well as randomized situs. In Ft mice a large chromosomal deletion (about 300 kb) occurred after insertional mutagenesis. In this report we describe the identification of the first gene that has been mutated by Fused toes. The expression of the novel gene Ft1 is reduced in Ft/+ mice and com

TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.

Previously we described joining of DNA in the beta T cell receptor gene to DNA of an uncharacterized locus in a t(7;9)(q34;q34.3) chromosomal translocation from a case of human T lymphoblastic leukemia (T-ALL). We now show that the locus on chromosome 9 contains a gene highly homologous to the Drosophila gene Notch. Transcripts of the human gene, for which we propose the name TAN-1, and its murine counterpart are present in many normal human fetal and adult mouse tissues, but are most abundant in lymphoid tissues. In t(7;9)(q34;q34.3) translocations from three cases of T-ALL, the breakpoints o

Basigin is necessary for normal decidualization of human uterine stromal cells.

STUDY QUESTION: Does basigin (BSG) regulate human endometrial stromal cell (HESC) decidualization in vitro? SUMMARY ANSWER: BSG regulates H … n, signaling transduction and regulation, response to stimulus, cell adhesion, anatomical structure morphogenesis, extracellular matrix organization, as well as other functional pathways. KEGG pathway analysis identified upregulated gene enriched in pathways such as the MAPK signaling pathway, colorectal cancer, melanoma and axon guidance. In contrast, downregu …

Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.

STUDY QUESTION: What is the impact of chronic hypertension on placental development, fetal growth and maternal outcome in the stroke-prone s … (P < 0.01 versus WKY) and signs of placental insufficiency (i.e. hypertrophy and reduced branching morphogenesis of the labyrinth layer), associated with decreased offspring weights and increased cephalization index (both P < 0.001 versus WKY) indicating asymmetric FGR. Notably, SHRSP placentas displayed an incomplete remodeling of spiral arteries starting as …

Another look at human sperm morphology.

STUDY QUESTION: Can a standardized assessment of abnormal human sperm morphology provide additional useful information by identifying men wi … ticular cancer than in infertile men, highlighting the particular impact of this condition on sperm morphogenesis. We used the 95th percentile in fertile men as the lower threshold and the 99th percentile in infertile men as an extreme upper threshold, for the classification of morphological abnormality frequencies into three levels: low, intermediate and high. …

Transcriptome Analysis Reveals Altered Inflammatory Pathway in an Inducible Glial Cell Model of Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1), the most frequent inherited muscular dystrophy in adults, is caused by the CTG repeat expansion in the 3'UTR of the DMPK gene. Mutant DMPK RNA accumulates in nuclear foci altering diverse cellular functions including alternative splicing regulation. DM1 is a multisystemic condition, with debilitating central nervous system alterations. Although a defective neuroglia communication has been described as a contributor of the brain pathology in DM1, the specific cellular and molecular events potentially affected in glia cells have not been totally recognized. Thus,

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… Skeletal system morphogenesis Skeletal system development Anatomical structure morphogenesis Regulation of signal transduction | 1.3 × 10 −3 3.9 × 10 −3 4.0 × 10 −3 1.3 × 10 −2 1.6 × 10 −2 1.9 × 10 −2 Down-regulated: APLN, CD24, COL11A1, DCN, EYA1, GHR, HHAT, KIF26B, PLEKHS1, PLXDC1, PSD3, SCD, SV2A … We determined 32 putative miR-103a-1 targets, involved in animal organ development and morphogenesis. miR-298 revealed to have 24 targets enriched in anatomical structure morphogenesis, among other biological processes. miR-4310 showed 18 targets, that were associated with Toll-like receptor signaling …