piggyBac-based mosaic screen identifies a postmitotic function for cohesin in regulating developmental axon pruning.
نویسندگان
چکیده
Developmental axon pruning is widely used to refine neural circuits. We performed a mosaic screen to identify mutations affecting axon pruning of Drosophila mushroom body gamma neurons. We constructed a modified piggyBac vector with improved mutagenicity and generated insertions in >2000 genes. We identified two cohesin subunits (SMC1 and SA) as being essential for axon pruning. The cohesin complex maintains sister-chromatid cohesion during cell division in eukaryotes. However, we show that the pruning phenotype in SMC1(-/-) clones is rescued by expressing SMC1 in neurons, revealing a postmitotic function. SMC1(-/-) clones exhibit reduced levels of the ecdysone receptor EcR-B1, a key regulator of axon pruning. The pruning phenotype is significantly suppressed by overexpressing EcR-B1 and is enhanced by a reduced dose of EcR, supporting a causal relationship. We also demonstrate a postmitotic role for SMC1 in dendrite targeting of olfactory projection neurons. We suggest that cohesin regulates diverse aspects of neuronal morphogenesis.
منابع مشابه
Cell-Type-Specific TEV Protease Cleavage Reveals Cohesin Functions in Drosophila Neurons
Cohesin is a highly conserved multisubunit complex that holds sister chromatids together in mitotic cells. At the metaphase to anaphase transition, proteolytic cleavage of the alpha kleisin subunit (Rad21) by separase causes cohesin's dissociation from chromosomes and triggers sister-chromatid disjunction. To investigate cohesin's function in postmitotic cells, where it is widely expressed, we ...
متن کاملDevelopmental Axon Pruning Requires Destabilization of Cell Adhesion by JNK Signaling
Developmental axon pruning is essential for normal brain wiring in vertebrates and invertebrates. How axon pruning occurs in vivo is not well understood. In a mosaic loss-of-function screen, we found that Bsk, the Drosophila JNK, is required for axon pruning of mushroom body γ neurons, but not their dendrites. By combining in vivo genetics, biochemistry, and high-resolution microscopy, we demon...
متن کاملDoes cohesin regulate developmental gene expression in Drosophila?
C ohesin is a conserved protein complex with a well documented role in providing stable but reversible connections between sister chromatids during both mitosis and meiosis. Cohesin consists of two long coiled-coil proteins (SMC1 and SMC3) and two non-SMC subunits (SCC1/Rad21 and SCC3/SA) that combine to form a ring-like structure. Establishment, maintenance, and timely removal of cohesin-media...
متن کاملpiggyBac Insertional Mutagenesis Screen Identifies a Role for Nuclear RHOA in Human ES Cell Differentiation
The mechanisms regulating human embryonic stem (ES) cell self-renewal and differentiation are not well defined in part due to the lack of tools for forward genetic analysis. We present a piggyBac transposon gain of function screen in human ES cells that identifies DENND2C, which genetically cooperates with NANOG to maintain self-renewal in the presence of retinoic acid. We show that DENND2C neg...
متن کاملAlternative Functions of Core Cell Cycle Regulators in Neuronal Migration, Neuronal Maturation, and Synaptic Plasticity
Recent studies have demonstrated that boundaries separating a cycling cell from a postmitotic neuron are not as concrete as expected. Novel and unique physiological functions in neurons have been ascribed for proteins fundamentally required for cell cycle progression and control. These "core" cell cycle regulators serve diverse postmitotic functions that span various developmental stages of a n...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Developmental cell
دوره 14 2 شماره
صفحات -
تاریخ انتشار 2008