Stumpy cilia with malformed microtubules (top) mess up hedgehog signaling.


It takes well-built cilia to send developmental signals on their way, show Tamara Caspary, Kathryn Anderson (Sloan-Kettering Institute, New York, NY), and Christine Larkins (Emory University, Atlanta, GA). Cilia that lack the correct internal architecture fail to transduce Hedgehog (Hh) signals correctly.

Hh signaling is particularly well-characterized in the developing nervous system. Depending on the amount of Hh activity, different types of neurons are produced. The particular type of neuron that forms is a result of the combination and amount of Hh-induced Gli transcription factors.

Caspary et al. now show that this neuronal choice is impaired in a mouse mutant called hennin, which has stumpy cilia. In these animals, different Hh levels were unable to increase or decrease Gli2 activity, which was stuck at a constitutively low level. As a result, one particular type of neuron was preferentially produced.

It's not the shortness of the cilia that's to blame, however—other mutants with short cilia have normal Hh signaling—it's the cilia's internal structure. The hennin mice lacked a cilial protein called Arl13b, which appeared to be required for correct cilial microtubule architecture.

Gli2 has also been found in cilia. Given the intermediate level of Gli2 activity in the mutant mouse cells, the authors suggest that correct cilial architecture might be required for both activating and restricting Gli2 activity. Cilial microtubules might, for instance, be needed for processing Gli2 into a highly active form and also for tethering Gli2 to prevent its action when it is not needed.


Caspary, T., et al.
Dev. Cell.