The Dispatched ortholog, CHE-14, is dispensable for apical secretion of the Hedgehog-related proteins GRL-2 and WRT-10.

nematodes possess expanded families of Hedgehog related (Hh-r) and Patched/Dispatched-related (PTR) proteins but their functional relationship remains unclear. Here we investigated whether CHE-14 , the closest ortholog for the Hedgehog transporter Dispatched, was necessary for the secretion of two tagged Hh-r proteins: WRT-10 and GRL-2 . We report that CHE-14 is dispensable for the apical localization of GRL-2 and WRT-10 .

Caenorhabditis elegans Hedgehog-related proteins are tissue- and substructure-specific components of the cuticle and precuticle.

In Caenorhabditis elegans, expanded families of divergent Hedgehog-related and patched-related proteins promote numerous processes ranging from epithelial and sense organ development to pathogen responses to cuticle shedding during the molt cycle. The molecular functions of these proteins have been mysterious since nematodes lack a canonical Hedgehog signaling pathway. Here we show that Hedgehog-related proteins are components of the cuticle and precuticle apical extracellular matrices that coat, shape, and protect external epithelia.

Hedgehog-related proteins are tissue- and substructure-specific components of the cuticle and pre-cuticle.

In , divergent Hedgehog-related (Hh-r) and Patched-related (PTR) proteins promote numerous processes ranging from epithelial and sense organ development to pathogen responses to cuticle shedding during the molt cycle. Here we show that Hh-r proteins are actual components of the cuticle and pre-cuticle apical extracellular matrices (aECMs) that coat, shape, and protect external epithelia. Different Hh-r proteins stably associate with the aECMs of specific tissues and with specific substructures such as furrows and alae.

Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD+ salvage pathway mutant.

Necrosis was once described as a chaotic unregulated response to cellular insult. We now know that necrosis is controlled by multiple pathways in response to many different cellular conditions. In our pnc-1 NAD+ salvage deficient Caenorhabditis elegans model excess nicotinamide induces excitotoxic death in uterine-vulval uv1 cells and OLQ mechanosensory neurons.

The Caenorhabditis elegans Patched domain protein PTR-4 is required for proper organization of the precuticular apical extracellular matrix.

The Patched-related superfamily of transmembrane proteins can transport lipids or other hydrophobic molecules across cell membranes. While the Hedgehog receptor Patched has been intensively studied, much less is known about the biological roles of other Patched-related family members. Caenorhabditis elegans has a large number of Patched-related proteins, despite lacking a canonical Hedgehog pathway.

Transcytosis in the development and morphogenesis of epithelial tissues.

Transcytosis is a form of specialized transport through which an extracellular cargo is endocytosed, shuttled across the cytoplasm in membrane-bound vesicles, and secreted at a different plasma membrane surface. This important process allows membrane-impermeable macromolecules to pass through a cell and become accessible to adjacent cells and tissue compartments. Transcytosis also promotes redistribution of plasma membrane proteins and lipids to different regions of the cell surface.

The rapamycin analog Everolimus reversibly impairs male germ cell differentiation and fertility in the mouse†.

Sirolimus, also known as rapamycin, and its closely related rapamycin analog (rapalog) Everolimus inhibit "mammalian target of rapamycin complex 1" (mTORC1), whose activity is required for spermatogenesis. Everolimus is Food and Drug Administration approved for treating human patients to slow growth of aggressive cancers and preventing organ transplant rejection. Here, we test the hypothesis that rapalog inhibition of mTORC1 activity has a negative, but reversible, impact upon spermatogenesis.

Differential RA responsiveness directs formation of functionally distinct spermatogonial populations at the initiation of spermatogenesis in the mouse.

In the mammalian testis, sustained spermatogenesis relies on spermatogonial stem cells (SSCs); their progeny either remain as stem cells (self-renewal) or proliferate and differentiate to enter meiosis in response to retinoic acid (RA). Here, we sought to uncover elusive mechanisms regulating a key switch fundamental to spermatogonial fate: the capacity of spermatogonia to respond to RA. Using the developing mouse testis as a model, we found that spermatogonia and precursor prospermatogonia exhibit a heterogeneous capacity to respond to RA with at least two underlying causes.

Dynamic cytoplasmic projections connect mammalian spermatogonia .

Throughout the male reproductive lifespan, spermatogonial stem cells (SSCs) produce committed progenitors that proliferate and then remain physically connected in growing clones via short cylindrical intercellular bridges (ICBs). These ICBs, which enlarge in meiotic spermatocytes, have been demonstrated to provide a conduit for postmeiotic haploid spermatids to share sex chromosome-derived gene products. In addition to ICBs, spermatogonia exhibit multiple thin cytoplasmic projections.

Cell-autonomous requirement for mammalian target of rapamycin (Mtor) in spermatogonial proliferation and differentiation in the mouse†.

Spermatogonial stem cells must balance self-renewal with production of transit-amplifying progenitors that differentiate in response to retinoic acid (RA) before entering meiosis. This self-renewal vs. differentiation fate decision is critical for maintaining tissue homeostasis, as imbalances cause defects that can lead to human testicular cancer or infertility.