The biotin-ligating protein BPL-1 is critical for lipid biosynthesis and polarization of the embryo.

Biotin is an essential cofactor for multiple metabolic reactions catalyzed by carboxylases. Biotin is covalently linked to apoproteins by holocarboxylase synthetase (HCS). Accordingly, some mutations in HCS cause holocarboxylase deficiency, a rare metabolic disorder that can be life-threatening if left untreated.

High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence.

Quiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying matrix cells. EPs can revert to SCs upon injury, but whether this dedifferentiation occurs in normal HF homeostasis (hair cycle) and the mechanisms regulating both differentiation and dedifferentiation are unclear. Here, we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle.

Small molecule injection into single-cell C. elegans embryos via carbon-reinforced nanopipettes.

The introduction of chemical inhibitors into living cells at specific times in development is a useful method for investigating the roles of specific proteins or cytoskeletal components in developmental processes. Some embryos, such as those of Caenorhabditis elegans, however, possess a tough eggshell that makes introducing drugs and other molecules into embryonic cells challenging. We have developed a procedure using carbon-reinforced nanopipettes (CRNPs) to deliver molecules into C.

Deubiquitylation machinery is required for embryonic polarity in Caenorhabditis elegans.

The Caenorhabditis elegans one-cell embryo polarizes in response to a cue from the paternally donated centrosome and asymmetrically segregates cell fate determinants that direct the developmental program of the worm. We have found that genes encoding putative deubiquitylating enzymes (DUBs) are required for polarization of one-cell embryos. Maternal loss of the proteins MATH-33 and USP-47 leads to variable inability to correctly establish and maintain asymmetry as defined by posterior and anterior polarity proteins PAR-2 and PAR-3.

A genome-wide RNAi screen for enhancers of par mutants reveals new contributors to early embryonic polarity in Caenorhabditis elegans.

The par genes of Caenorhabditis elegans are essential for establishment and maintenance of early embryo polarity and their homologs in other organisms are crucial polarity regulators in diverse cell types. Forward genetic screens and simple RNAi depletion screens have identified additional conserved regulators of polarity in C. elegans; genes with redundant functions, however, will be missed by these approaches.

Control of mitotic and meiotic centriole duplication by the Plk4-related kinase ZYG-1.

Centriole duplication is of crucial importance during both mitotic and male meiotic divisions, but it is currently not known whether this process is regulated differently during the two modes of division. In Caenorhabditis elegans, the kinase ZYG-1 plays an essential role in both mitotic and meiotic centriole duplication. We have found that the C-terminus of ZYG-1 is necessary and sufficient for targeting to centrosomes and is important for differentiating mitotic and meiotic centriole duplication.

Binding to PKC-3, but not to PAR-3 or to a conventional PDZ domain ligand, is required for PAR-6 function in C. elegans.

PAR-6 is a conserved protein important for establishment and maintenance of cell polarity in a variety of metazoans. PAR-6 proteins function together with PAR-3, aPKC and CDC-42. Mechanistic details of their interactions, however, are not fully understood.

Interaction of PAR-6 with CDC-42 is required for maintenance but not establishment of PAR asymmetry in C. elegans.

Caenorhabditis elegans embryonic polarity requires the asymmetrically distributed proteins PAR-3, PAR-6 and PKC-3. The rho family GTPase CDC-42 regulates the activities of these proteins in mammals, flies and worms. To clarify its mode of action in C.

PAR-3 is required for epithelial cell polarity in the distal spermatheca of C. elegans.

PAR-3 is localized asymmetrically in epithelial cells in a variety of animals from Caenorhabditis elegans to mammals. Although C. elegans PAR-3 is known to act in early blastomeres to polarize the embryo, a role for PAR-3 in epithelial cells of C.

PAR-1 is required for morphogenesis of the Caenorhabditis elegans vulva.

The Caenorhabditis elegans vulva provides a simple model for the genetic analysis of pattern formation and organ morphogenesis during metazoan development. We have discovered an essential role for the polarity protein PAR-1 in the development of the vulva. Postembryonic RNA interference of PAR-1 causes a protruding vulva phenotype.

Gene clustering based on RNAi phenotypes of ovary-enriched genes in C. elegans.

Recently, a set of 766 genes that are enriched in the ovary as compared to the soma was identified by microarray analysis [1]. Here, we report a functional analysis of 98% of these genes by RNA interference (RNAi). Over half the genes tested showed at least one detectable phenotype, most commonly embryonic lethality, consistent with the expectation that ovary transcripts would be enriched for genes that are essential in basic cellular and developmental processes.

Integrating interactome, phenome, and transcriptome mapping data for the C. elegans germline.

By integrating functional genomic and proteomic mapping approaches, biological hypotheses should be formulated with increasing levels of confidence. For example, yeast interactome and transcriptome data can be correlated in biologically meaningful ways. Here, we combine interactome mapping data generated for a multicellular organism with data from both large-scale phenotypic analysis ("phenome mapping") and transcriptome profiling.

The Caenorhabditis elegans par-5 gene encodes a 14-3-3 protein required for cellular asymmetry in the early embryo.

The establishment of anterior-posterior polarity in the Caenorhabditis elegans embryo requires the activity of the maternally expressed par genes. We report the identification and analysis of a new par gene, par-5. We show that par-5 is required for asynchrony and asymmetry in the first embryonic cell divisions, normal pseudocleavage, normal cleavage spindle orientation at the two-cell stage, and localization of P granules and MEX-5 during the first and subsequent cell cycles.