Kartagener's

Question 1

what is happening?

Answer 1

problems with cilia and turns out cilia is responsible for L-R patterning
results from mutations in proteins that constitute dynein arms of cilia

Question 2

Describe the genetic origins of Kartagener’s syndrome, or primary ciliary dyskinesia (PCD), and heterotaxy.

Answer 2

Around 90% of mutations underlying PCD are found in genes encoding proteins of the outer and/or inner dynein arms which give cilia their motility. Heterotaxy is much more heterogeneous, where mutations have been identified in genes involved in various signaling pathways, including TGFb signaling and nodal signaling.

Question 3

What key signaling pathways are involved in PCD?

Answer 3

Nodal and sonic hedgehog signaling.

Question 4

What key factors are involved in early left-right patterning?

Answer 4

Nodal, Lefty2 and Pitx2.

Question 5

Describe the two main models describing the initiation of left-right patterning.

Answer 5

The morphogen flow hypothesis suggests that a critical signaling molecule, or morphogen, is released symmetrically into the node region and subsequently becomes concentrated to the left side of the node in response to nodal flow generated by the rotation of motile node cilia. The two-cilia model suggests that nodal flow generated by the activity of motile node cilia produces differential fluid pressure at the two sides of the node, leading to asymmetric stimulation of mechanosensory cilia distributed symmetrically in the node region. In response to stimulation, these mechanosensory cilia initiate a calcium-mediated signal transduction event that leads to the asymmetric induction of Nodal and other left-sided genes. (See Tabin & Vogan, Genes & Development, 2003.)