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Sall1 regulates neuronal differentiation and progenitor cell maturation in the developing forebrain

by Harrison, Susan J.

Abstract (Summary)
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.
Bibliographical Information:

Advisor:Cynthia Lance-Jones; Neil Hukriede; A. Paula Monaghan; Martin Schmidt; Edda Thiels

School:University of Pittsburgh

School Location:USA - Pennsylvania

Source Type:Master's Thesis

Keywords:biochemistry and molecular genetics

ISBN:

Date of Publication:10/04/2007

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