The zinc finger transcription factor Gata2 has been suggested to play a variety of roles in selected populations within the developing and mature nervous system. Here I show that Gata2 is involved in early neural differentiation and migration in the embryonic midbrain and that it is also selectively expressed within several mature neuronal midbrain structures. To evaluate the developmental context of Gata2 expression, I performed immunohistochemical localization of Gata2 protein as well as other fate markers in rat brain over a range of developmental stages. The protein is widely expressed throughout the developing midbrain and certain regions of the thalamus starting as early as e13 – initially ventrally and then occupying the entire circumference of the midbrain by e15. This expression is always limited to the intermediate zone, where the Gata2-expressing cells can be seen directly beneath the TUJ1-positive neuronal layer and just superficial to the proliferative ventricular zone. It appears that these Gata2+ cells are very early migrating neurons, and consistent with this interpretation, in the dorsal midbrain I observe co-expression with the proneural gene Mash1 in approximately 35% of the population; the majority of double-positive cells being those closest to the ventricle. Later in development from e17 onward, Gata2 was also expressed by several distinct mature neuronal populations within the midbrain. To better understand the developmental role of Gata2 in the midbrain, I carried out in utero electroporation of e16 rat dorsal midbrain to achieve either shRNA-mediated knockdown of Gata2 or constitutive Gata2 expression. siRNA-mediated knockdown of transient expression in dorsal mesencephalon resulted in migration arrest of migrating precursor cells in the deep layers of the superior colliculus. A higher proportion of these migration arrested cells also expressed immature markers, suggesting that they exhibited retarded or suppressed neuronal differentiation. In conclusion, I provide evidence that Gata2 is required for normal midbrain development and that it may exert an important role in migration and differentiation of immature neurons within this structure.
|Advisor:||Greene, Lloyd A.|
|School Location:||United States -- New York|
|Source:||DAI-B 72/05, Dissertation Abstracts International|
|Keywords:||Central nervous system, Neural migration, Neuronal differentiation, Peripheral nervous system, Superior colliculus|
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