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BMP-mediated cis-regulation of msh/msx genes in Drosophila and vertebrates /


In a broad variety of bilaterian species the trunk central nervous system (CNS) derives from three primary rows of neuroblasts. The fates of these three rows of neuroblasts are determined in part by the expression of three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal- ventral axis. While this conserved suite of "neural identity" gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved. In Drosophila, genetic evidence suggests that BMPs act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this thesis I contributed to the analysis of mechanisms by which BMPs act on cis-regulatory modules (CRMs) that control localized expression of the Drosophila msh and zebrafish msxB in the dorsal CNS. My studies helped confirm that BMPs regulate neural genes in a threshold dependent manner and support the view that BMPs act differently to regulate similar patterns of gene expression in the neuroectoderm by repressing msh expression in Drosophila while activating msxB expression in zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two lineages

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