Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


ucin1163039225.pdf (9.38 MB)

ETD Abstract Container

Abstract Header

The role of Cdc42 and Rac1 GTPases in mammalian forebrain development

Chen, Lei
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1163039225

Abstract Details

2006, PhD, University of Cincinnati, Medicine : Molecular and Developmental Biology.
Rho family GTPases are key regulators of a variety of cell functions including actin cytoskeleton organization, gene transcription, cell cycle progression and vesicle trafficking. In the mammalian neuronal system the Rho family members Cdc42 and Rac1 have been suggested to play roles in neuronal morphogenesis and synaptic transmission in a body of literature that is derived by over-expression of dominant-negative or constitutive-active mutants in cell cultures or transgenic animals. To investigate the physiologic function of Cdc42 and Rac1 in mammalian neural development, we have applied a conditional gene targeting strategy by crossbreeding Foxg1-Cre gene targeted mice with Rac1 or Cdc42 gene floxed conditional strain to achieve the deletion of each gene specifically in the telencephalon. We found that Cdc42-deletion abolishes the polarity of neuroepithelial (NE) cells. Consequently, neural progenitors were scattered throughout the entire depth of the NE, and the Cdc42-deficient telencephalon failed to bulge or separate into two cerebral hemispheres resulting in holoprosencephaly. However, neither the midline expression of Sonic hedgehog nor the dorso-ventral patterning of the telencephalon was affected by Cdc42-deletion. These results indicate that Cdc42 has an essential role in establishing the apical-basal polarity of the telencephalic NE, which is needed for the expansion and bifurcation of cerebral hemispheres. In contrast to Cdc42 deletion, Rac1 deficiency in the forebrain does not affect the polarity of NE, but does cause a profound phenotype. The Rac1 deficient embryos exhibit defects in the midline commissural axon tract formation and the tangential migration of the olfactory and cortical interneurons. Unlike previous studies using dominant-negative mutants, deletion of Rac1 did not prevent axon outgrowth or radial migration of cortical projection neurons. Interestingly, the tangential migration was not affected by the ventral telencephalon SVZ-deletion of Rac1 in Dlx5/6-Cre/Rac1loxp/null mice. These results provide strong evidence that Rac1 is important in regulating axonal projection, but is dispensable for neuritogenesis per se. Furthermore, there appears a progenitor-specific requirement of Rac1 for the subsequent migration of ventral telencepahlon-derived interneurons. In summary, the collective results of the thesis studies suggest that Cdc42 and Rac1 have important but distinct roles during mammalian forebrain development.
Yi Zheng (Advisor)
127 p.
Rho GTPase; forebrain; development; neuritogenesis; axon guidance; migration; polarity; patterning; holoprosencephaly

Recommended Citations

Citations

  • Chen, L. (2006). The role of Cdc42 and Rac1 GTPases in mammalian forebrain development [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1163039225

    APA Style (7th edition)

  • Chen, Lei. The role of Cdc42 and Rac1 GTPases in mammalian forebrain development. 2006. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1163039225.

    MLA Style (8th edition)

  • Chen, Lei. "The role of Cdc42 and Rac1 GTPases in mammalian forebrain development." Doctoral dissertation, University of Cincinnati, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1163039225

    Chicago Manual of Style (17th edition)

ucin1163039225
562
© 2006, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.