@article {68758, title = {The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis}, journal = {Developmental Cell}, volume = {48}, year = {2019}, month = {03/2019}, pages = {864-872.e7}, abstract = {

Summary Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule\ coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C.\ elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis.

}, keywords = {Chromosome Segregation, dendrite, kinetochore, KMN network, Knl1, microtubule, Mis12 complex, Mitosis, Morphogenesis, Ndc80 complex, Nervous System, sensory neuron}, issn = {1534-5807}, doi = {https://doi.org/10.1016/j.devcel.2019.02.002}, url = {https://www.sciencedirect.com/science/article/pii/S1534580719300577}, author = {Dhanya K. Cheerambathur and Bram Prevo and Tiffany-Lynn Chow and Neil Hattersley and Shaohe Wang and Zhiling Zhao and Taekyung Kim and Adina Gerson-Gurwitz and Karen Oegema and Rebecca Green and Arshad Desai} } @article {68764, title = {A Small RNA-Catalytic Argonaute Pathway Tunes Germline Transcript Levels to Ensure Embryonic Divisions}, journal = {Cell}, volume = {165}, year = {2016}, month = {04/2016}, pages = {396-409}, abstract = {

Summary Multiple division cycles without growth are a characteristic feature of early embryogenesis. The female germline loads proteins and RNAs into oocytes to support these divisions, which lack many quality control mechanisms operating in somatic cells undergoing growth. Here, we describe a small RNA-Argonaute pathway that ensures early embryonic divisions in C.\ elegans by employing catalytic slicing activity to broadly tune, instead of silence, germline gene expression. Misregulation of one target, a kinesin-13 microtubule depolymerase, underlies a major phenotype associated with pathway loss. Tuning of target transcript levels is guided by the density of homologous small RNAs, whose generation must ultimately be related to target sequence. Thus, the tuning action of a small RNA-catalytic Argonaute pathway generates oocytes capable of supporting embryogenesis. We speculate that the specialized nature of germline chromatin led to the emergence of small RNA-catalytic Argonaute pathways in the female germline as a post-transcriptional control layer to optimize oocyte composition.

}, keywords = {22G RNA, Argonaute, Centromere, chromosome, CSR-1, embryogenesis, Fertility, germline, maternal load, Oogenesis, small RNA}, issn = {0092-8674}, doi = {https://doi.org/10.1016/j.cell.2016.02.040}, url = {https://www.sciencedirect.com/science/article/pii/S0092867416301908}, author = {Adina Gerson-Gurwitz and Shaohe Wang and Shashank Sathe and Rebecca Green and Gene~W. Yeo and Karen Oegema and Arshad Desai} } @article {68767, title = {The Microtubule Minus-End-Binding Protein Patronin/PTRN-1 Is Required for Axon Regeneration in C.~elegans}, journal = {Cell Reports}, volume = {9}, year = {2014}, month = {11/2014}, pages = {874-883}, abstract = {

Summary Precise regulation of microtubule (MT) dynamics is increasingly recognized as a critical determinant of\ axon regeneration. In contrast to developing neurons, mature axons exhibit noncentrosomal microtubule nucleation. The factors regulating noncentrosomal MT architecture in axon regeneration remain poorly understood. We report that PTRN-1, the C.\ elegans member of the Patronin/Nezha/calmodulin- and spectrin-associated protein (CAMSAP) family of microtubule minus-end-binding proteins, is critical for efficient axon regeneration in\ vivo. ptrn-1-null mutants display generally normal developmental axon outgrowth but significantly impaired regenerative regrowth after laser axotomy. Unexpectedly, mature axons in ptrn-1 mutants display elevated numbers of dynamic axonal MTs before and after injury, suggesting that PTRN-1 inhibits MT dynamics. The CKK domain of PTRN-1 is necessary and sufficient for its functions in axon regeneration and MT dynamics and appears to stabilize MTs independent of minus-end localization. Whereas in developing neurons, PTRN-1 inhibits activity of the DLK-1 mitogen-activated protein kinase (MAPK) cascade, we find that, in regeneration, PTRN-1 and DLK-1 function together to promote axonal regrowth.

}, issn = {2211-1247}, doi = {https://doi.org/10.1016/j.celrep.2014.09.054}, url = {https://www.sciencedirect.com/science/article/pii/S2211124714008377}, author = {Marian Chuang and Alexandr Goncharov and Shaohe Wang and Karen Oegema and Yishi Jin and Andrew~D. Chisholm} }