HEM-protein regulates cell migration and asymmetric cell division during development of the ventral nerve cord in Drosophila melanogaster

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Title: HEM-protein regulates cell migration and asymmetric cell division during development of the ventral nerve cord in Drosophila melanogaster
Author: Zengrong Zhu
Abstract: Cell migration and asymmetric cell division are two of the key events during development of the nervous system . I have focused on a typical neuronal lineage , NB4 -2→GMC -1→RP2 /sib , in the ventral nerve cord (VNC ) of the Drosophila embryo to investigate the regulation of neuronal migration and asymmetric cell division during development of the nervous system . I have discovered a migration defect of RP2 neurons in HEM -protein (Hem ) mutants : RP2 neurons cross the midline and migrate from the initial hemi -segment to the opposite hemi -segment . The same migration defect is observed in WASP -family verprolin -homologous protein (WAVE /SCAR ) and Abl tyrosine kinase (Abl ) mutants , suggesting that these three genes might act together to regulate neuronal migration in the VNC . I have found that Hem is required for maintaining the protein level of WAVE in vivo and is necessary for its proper localization in the cell . In Hem mutants , WAVE is down regulated and mis -localized in RP2 neurons , resulting in the migration defect of RP2 neurons . Abl on the other hand negatively regulates the protein level of WAVE . When Abl is ectopically expressed , WAVE protein is down regulated . In Abl mutants , WAVE is up regulated and its hyperactivity may be responsible for the migration defect of RP2 neurons . Meanwhile , instead of asymmetric division in wild type embryos , a symmetric division of GMC -1 is observed in the “strong phenotype embryo†of HemJ4 -48 mutants . It was not observed in other Hem mutants and Hem deficiency alleles . The truncated Hem protein (∆HemJ4 -48 ) in HemJ4 -48 allele may behave as a neomorphic protein , resulting in the symmetric division of GMC -1 . In HemJ4 -48 mutants , the apical localization of Inscuteable (Insc ) is disrupted , suggesting that regulation of the asymmetric division of GMC -1 by Hem is mediated by Insc . The same symmetric division of GMC -1s was also observed in Abl mutants but not WAVE mutants , suggesting that Abl may act together with Hem to regulate the asymmetric division of GMC -1s . This study uses the Drosophila VNC as a model system and describes how neuronal migration and asymmetric cell division are regulated by Hem during development of the nervous system .
URI: http : / /hdl .handle .net /2152 .3 /202
Date: 2010-07-08

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HEM-protein regulates cell migration and asymmetric cell division during development of the ventral nerve cord in Drosophila melanogaster. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /202 .

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