Organogenesis: keeping in touch with the germ cells

AbstractDE-cadherin and its novel regulator, the transmembrane protein Fear of Intimacy, have been found to control the adhesive interactions between germline and somatic cells that lead to gonad formation in Drosophila

The NEMP family supports metazoan fertility and nuclear envelope stiffness.

Human genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in NEMP1 (nuclear envelope membrane protein 1) with early menopause; however, it is unclear whether NEMP1 has any role in fertility. We show that whole-animal loss of NEMP1 homologs in Drosophila, Caenorhabditis elegans, zebrafish, and mice leads to sterility or early loss of fertility. Loss of Nemp leads to nuclear shaping defects, most prominently in the germ line. Biochemical, biophysical, and genetic studies reveal that NEMP proteins support the mechanical stiffness of the germline nuclear envelope via formation of a NEMP-EMERIN complex. These data indicate that the germline nuclear envelope has specialized mechanical properties and that NEMP proteins play essential and conserved roles in fertility

Integration of Migratory Cells into a New Site In Vivo Requires Channel-Independent Functions of Innexins on Microtubules

During embryonic development and cancer metastasis, migratory cells must establish stable connections with new partners at their destinations. Here, we establish the Drosophila border cells as a model for this multistep process. During oogenesis, border cells delaminate from the follicular epithelium and migrate. When they reach their target, the oocyte, they undergo a stereotypical series of steps to adhere to it, then connect with another migrating epithelium. We identify gap-junction-forming innexin proteins as critical. Surprisingly, the channel function is dispensable. Instead, Innexins 2 and 3 function within the border cells, and Innexin 4 functions within the germline, to regulate microtubules. The microtubule-dependent border cell-oocyte interaction is essential to brace the cells against external morphogenetic forces. Thus, we establish an experimental model and use genetic, thermogenetic, and live-imaging approaches to uncover the contributions of Innexins and microtubules to a cell-biological process important in development and cancer

The Drosophila melanogaster BTB proteins bric à brac bind DNA through a composite DNA binding domain containing a pipsqueak and an AT-Hook motif

The bric à brac (bab) locus is composed of two paralogous genes, bab1 and bab2, in Drosophila melanogaster. Bab1 and Bab2 are nuclear proteins that contain a broad complex, tramtrack, bric à brac/poxviruses and zinc-finger (BTB/POZ) domain. Many BTB/POZ proteins are transcriptional regulators of which the majority contain C(2)H(2) zinc-finger motifs. There is no detectable zinc-finger motif in either Bab protein. However, they share the Bab conserved domain (BabCD) that is highly conserved between Bab1 and Bab2, and the Bab proteins of several other species, e.g. Anopheles gambiae, Apis mellifera and Drosophila virilis. Here we show that Bab2 binds to several discrete sites on polytene chromosomes including the bab locus, and that the BabCD of both Bab1 and Bab2 binds in vitro to the cis-regulatory regions of bab1 and bab2. Our results indicate that the BabCD binds to A/T-rich regions and that its optimum binding sites contain TA or TAA repeats. The BabCD is a composite DNA binding domain with a psq motif and an AT-Hook motif; both motifs are required for DNA binding activity. Structural similarities suggest that the BabCD may bind to DNA in a similar manner as some prokaryotic recombinases

The germline stem cells of Drosophila melanogaster partition DNA non-randomly

The Immortal Strand Hypothesis proposes that asymmetrically dividing stem cells cosegregate chromatids to retain ancestral DNA templates. Using both pulse-chase and label retention assays, we show that non-random partitioning of DNA occurs in germline stem cells (GSCs) in the Drosophila ovary as these divide asymmetrically to generate a new GSC and a differentiating cystoblast. This process is disrupted when GSCs are forced to differentiate through the overexpression of Bag of Marbles, a factor that impels the terminal differentiation of cystoblasts. When Decapentaplegic, a ligand which maintains the undifferentiated state of GSCs, is expressed ectopically the non-random partitioning of DNA is similarly disrupted. Our data suggest asymmetric chromatid segregation is coupled to mechanisms specifying cellular differentiation via asymmetric stem cell division

The bric à brac locus consists of two paralogous genes encoding BTB/POZ domain proteins and acts as a homeotic and morphogenetic regulator of imaginal development in Drosophila.

The bric a brac (bab) locus acts as a homeotic and morphogenetic regulator in the development of ovaries, appendages and the abdomen. It consists of two structurally and functionally related genes, bab1 and bab2, each of which encodes a single nuclear protein. Bab1 and Bab2 have two conserved domains in common, a BTB/POZ domain and a Psq domain, a motif that characterizes a subfamily of BTB/POZ domain proteins in DROSOPHILA: The tissue distribution of Bab1 and Bab2 overlaps, with Bab1 being expressed in a subpattern of Bab2. Analysis of a series of mutations indicates that the two bab genes have synergistic, distinct and redundant functions during imaginal development. Interestingly, several reproduction-related traits that are sexually dimorphic or show diversity among Drosophila species are highly sensitive to changes in the bab gene dose, suggesting that alterations in bab activity may contribute to evolutionary modification of sex-related morphology

Specification and spatial arrangement of cells in the germline stem cell niche of the <i>Drosophila</i> ovary depend on the Maf transcription factor Traffic jam

<div><p>Germline stem cells in the <i>Drosophila</i> ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj) is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2–3 germline stem cells. In particular, we focused on the question of how cap cells form. Cap cells express Tj and are considered the key component of a mature germline stem cell niche. We conclude that Tj controls the specification of cap cells, as the complete loss of Tj function caused the development of additional terminal filament cells at the expense of cap cells, and terminal filament cells developed cap cell characteristics when induced to express Tj. Further, we propose that Tj controls the morphogenetic behavior of cap cells as they adopted the shape and spatial organization of terminal filament cells but otherwise appeared to retain their fate when Tj expression was only partially reduced. Our data indicate that Tj contributes to the establishment of germline stem cells by promoting the cap cell fate, and controls the stem cell-carrying capacity of the niche by regulating niche architecture. Analysis of the interactions between Tj and the Notch (N) pathway indicates that Tj and N have distinct functions in the cap cell specification program. We propose that formation of cap cells depends on the combined activities of Tj and the N pathway, with Tj promoting the cap cell fate by blocking the terminal filament cell fate, and N supporting cap cells by preventing the escort cell fate and/or controlling the number of cap cell precursors.</p></div