Sall1 is a zinc finger containing putative transcription factor that is robustly expressed during mammalian embryogenesis. In humans, the developmental disorder Townes Brocks Syndrome is associated with mutations in the SALL1 gene. Sall1-deficient animals die at birth due to kidney deficits; however, its function in the nervous system has not been characterized. During embryonic development Sall1 is expressed by cortical progenitor cells. In late embryonic and postnatal stages Sall1 is expressed by oligodendrocytes and glia, as well as regions of adult neurogenesis. In the absence of Sall1 forebrain derived structures, the cerebral cortex and olfactory bulbs, were specifically decreased in size, while no gross alterations in midbrain development was observed. This study investigated the cellular mechanisms of Sall1 function in the developing cortex. Alterations in progenitor cell number and the rate of neuronal differentiation were observed during cortical development in Sall1-mutant animals compared to controls. In the absence of Sall1 more cells are committed to early-born cortical structures, at the expense of the progenitor population. In addition, from mid-neurogenesis fewer cells are committed to later-born structures. Together, these findings suggest that early in development Sall1 promotes a progenitor state, and from mid-neurogenesis Sall1 promotes a neural fate. Furthermore, I propose that Sall1 regulates the transition from an early cortical progenitor cell to an intermediate progenitor cell. These findings suggest that Sall1 regulates cortical neurogenesis and progenitor cell maturation in the developing cortex.
Sall1 is also expressed by peripheral and central components of the developing olfactory system. Alterations in neurogenesis and mitral cell production were observed in Sall1-deficient olfactory bulbs. In addition, the olfactory nerve failed to extend past the ventral-medial region of the olfactory bulb in Sall1-mutant animals. Intrinsic patterns of neurogenesis were observed during olfactory development in control animals and in Sall1-mutant animals, these patterns of neurogenesis were disrupted. These findings suggest a role for Sall1 in regulating neuronal differentiation and maturation in the developing olfactory system. Together, these findings suggest a conserved role for Sall1 in regulating neurogenesis and cellular maturation in the developing cortex and olfactory bulb.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-10032007-134815 |
| Date | 04 October 2007 |
| Creators | Harrison, Susan J. |
| Contributors | Cynthia Lance-Jones, Neil Hukriede, A. Paula Monaghan, Martin Schmidt, Edda Thiels |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-10032007-134815/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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