157 research outputs found
VANG-1 and PRKL-1 Cooperate to Negatively Regulate Neurite Formation in Caenorhabditis elegans
Neuritogenesis is a critical early step in the development and maturation of neurons and neuronal circuits. While extracellular directional cues are known to specify the site and orientation of nascent neurite formation in vivo, little is known about the genetic pathways that block inappropriate neurite emergence in order to maintain proper neuronal polarity. Here we report that the Caenorhabditis elegans orthologues of Van Gogh (vang-1), Prickle (prkl-1), and Dishevelled (dsh-1), core components of planar cell polarity (PCP) signaling, are required in a subset of peripheral motor neurons to restrict neurite emergence to a specific organ axis. In loss-of-function mutants, neurons display supernumerary neurites that extend inappropriately along the orthogonal anteroposterior (A/P) body axis. We show that autonomous and non-autonomous gene activities are required early and persistently to inhibit the formation or consolidation of growth cone protrusions directed away from organ precursor cells. Furthermore, prkl-1 overexpression is sufficient to suppress neurite formation and reorient neuronal polarity in a vang-1– and dsh-1–dependent manner. Our findings suggest a novel role for a PCP–like pathway in maintaining polarized neuronal morphology by inhibiting neuronal responses to extrinsic or intrinsic cues that would otherwise promote extraneous neurite formation
Genetic evidence that Celsr3 and Celsr2, together with Fzd3, regulate forebrain wiring in a Vangl-independent manner
Sperm protein 17 is expressed in human nervous system tumours
BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),. RESULTS: A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells
Wnt5a Regulates Midbrain Dopaminergic Axon Growth and Guidance
During development, precise temporal and spatial gradients are responsible for
guiding axons to their appropriate targets. Within the developing ventral
midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain
targets remain to be fully elucidated. Wnts are morphogens that have been
identified as axon guidance molecules. Several Wnts are expressed in the VM
where they regulate the birth of DA neurons. Here, we describe that a precise
temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal
projections by VM DA neurons. In mice at E11.5, Wnt5a is
expressed in the VM where it was found to promote DA neurite and axonal growth
in VM primary cultures. By E14.5, when DA axons are approaching their striatal
target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM
explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is
capable of repelling DA neurites. Antagonism experiments revealed that the
effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase,
Rac1 (a component of the non-canonical Wnt planar cell polarity pathway).
Moreover, the effects were specific as they could be blocked by Wnt5a antibody,
sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further
verified in Wnt5a−/− mice, where
fasciculation of the medial forebrain bundle (MFB) as well as the density of DA
neurites in the MFB and striatal terminals were disrupted. Thus, our results
identify a novel role of Wnt5a in DA axon growth and guidance
Adolescent pregnancies in the Amazon Basin of Ecuador: a rights and gender approach to adolescents' sexual and reproductive health
In the Andean region of Latin America over one million adolescent girls get pregnant every year. Adolescent pregnancy (AP) has been associated with adverse health and social outcomes, but it has also been favorably viewed as a pathway to adulthood. AP can also be conceptualized as a marker of inequity, since it disproportionately affects girls from the poorest households and those who have not been able to attend school
Platelet-derived growth factor A-chain gene transcription is mediated by positive and negative regulatory regions in the promoter
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