Kuzbanian is a crucial member of the ADAM family of metalloproteinases. Kuzbanian-mediated cleavage of Notch represents in fact one of the fundamental steps leading to activation of the Notch pathway during early neurogenesis. This enzyme also plays important roles in later stages of neural development, modulating axon guidance and extension. Planarians are a model system well known for regenerative potential. These characteristics depend on a population of adult stem cells that guarantees replacement of all differentiated cell types, including nerve cells. Here we report the functional characterization of a planarian Kuzbanian-like gene (Smed-kuzbanian3). Smed-kuzbanian3 is expressed in the mesenchyme and in the central nervous system (CNS) and is overexpressed during regeneration of this structure. Functional ablation of Smed-kuzbanian3 by RNAi causes abnormal CNS regeneration. Anomalous eye morphogenesis, including atypical axonal projections of the optic chiasm, is observed. The architecture of the regenerating cephalic ganglia also appears unusual, with an aberrant number and distribution of nerve cells. We speculate that Smed-Kuzbanian3, similarly to that observed in other organisms, plays different roles during CNS regeneration. To test whether Smed-kuzbanian3 plays a conserved role during neurogenesis we plan to use Xenopus laevis embryos as a model system. Gain of function experiments will allow us to demonstrate the involvement of Smed-kuzbanian3 in modulating early Notch-mediated lateral inhibition mechanisms and the guidance of axonal extensions at later developmental stages.
A planarian kuzbanian-like gene is a key regulator during regeneration of the nervous system
ISOLANI, MARIA EMILIA;MARRACCI, SILVIA;BALESTRINI, LINDA;DERI, PAOLO;BATISTONI, RENATA
2014-01-01
Abstract
Kuzbanian is a crucial member of the ADAM family of metalloproteinases. Kuzbanian-mediated cleavage of Notch represents in fact one of the fundamental steps leading to activation of the Notch pathway during early neurogenesis. This enzyme also plays important roles in later stages of neural development, modulating axon guidance and extension. Planarians are a model system well known for regenerative potential. These characteristics depend on a population of adult stem cells that guarantees replacement of all differentiated cell types, including nerve cells. Here we report the functional characterization of a planarian Kuzbanian-like gene (Smed-kuzbanian3). Smed-kuzbanian3 is expressed in the mesenchyme and in the central nervous system (CNS) and is overexpressed during regeneration of this structure. Functional ablation of Smed-kuzbanian3 by RNAi causes abnormal CNS regeneration. Anomalous eye morphogenesis, including atypical axonal projections of the optic chiasm, is observed. The architecture of the regenerating cephalic ganglia also appears unusual, with an aberrant number and distribution of nerve cells. We speculate that Smed-Kuzbanian3, similarly to that observed in other organisms, plays different roles during CNS regeneration. To test whether Smed-kuzbanian3 plays a conserved role during neurogenesis we plan to use Xenopus laevis embryos as a model system. Gain of function experiments will allow us to demonstrate the involvement of Smed-kuzbanian3 in modulating early Notch-mediated lateral inhibition mechanisms and the guidance of axonal extensions at later developmental stages.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
