The Tumor-Associated Calcium Signal Transducer 2 (TACSTD2) oncogene is upregulated in cystic epithelial cells revealing a potential new target for polycystic kidney disease.

Polycystic kidney disease (PKD) is an important cause of kidney failure, but treatment options are limited. While later stages of the disease have been extensively studied, mechanisms driving the initial conversion of kidney tubules into cysts are not understood. To identify genes with the potential to promote cyst initiation, we deleted polycystin-2 (Pkd2) in mice and surveyed transcriptional changes before and immediately after cysts developed.

Two functional forms of the Meckel-Gruber syndrome protein TMEM67 generated by proteolytic cleavage by ADAMTS9 mediate Wnt signaling and ciliogenesis.

mutations are the major cause of Meckel-Gruber syndrome. TMEM67 is involved in both ciliary transition zone assembly, and non-canonical Wnt signaling mediated by its extracellular domain. How TMEM67 performs these two separate functions is not known.

Inpp5e Is Critical for Photoreceptor Outer Segment Maintenance.

In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouse Inpp5e where the gene was deleted either during outer segment formation or after outer segments were fully formed.

Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.

The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodopsin, whose outer segment trafficking involves intraflagellar transport (IFT).

Cilia Structure and Function in Human Disease.

Ciliary dysfunction causes a large group of developmental and degenerative human diseases known as ciliopathies. These diseases reflect the critical roles that cilia play in sensing the environment and in force generation for motility. Sensory functions include our senses of vision and olfaction.