Introduction 1835 1954 1957 1956 1961 1962 1963 1987 1987 1985 1988 1995 2007 The mechanism of ciliary motility and primary ciliary dyskinesia 1985 1 Fig. 1 asterisk arrowhead arrow  2006 2004 DNAH5 2002 Chlamydomonas 2007 Hydin 2008 HYDIN 2006 2003 1999 2005 2004 2006 2005 Principles of ciliogenesis Chlamydomonas 2002 2003 2003 1989 1991 1969 1971 1971 0 2008 2008 Ciliopathies Tg737 orpk Chlamydomonas 2000 2001 2+ 2002 2002 2007 2007 1988 1995 2005 2007 2007 2008 2006 2006 2007 2007 Tg737 2 2008 Fig. 2 arrows Ptc Red green DAPI blue Ptc Smo Asterisk 2008  Primary cilia in adult tissues Primary cilia persist in many differentiated cells, including kidney tubule epithelial cells, fibroblasts and neurons, after organogenesis is complete and cell division rates fall. Presumably, as semipermanent structures, the cilia function as mechano- or chemosensors and as a cellular global positioning system to detect changes in the surrounding environment, to initiate cellular replacement after damage, for example. To test this hypothesis, techniques are being used to knock out primary cilia or ciliary proteins in specific tissues of adult organisms. 2007 2007 One adult tissue responds immediately to ciliary knockout however—that is nervous tissue, most specifically neurons in the hypothalamus. Knockout of all adult primary cilia in the mouse, or specifically only of primary cilia on POMC neurons, leads to hyperphagia—compulsive and excessive eating—leading to obesity. Obesity then causes numerous secondary defects resembling type II diabetes. These defects do not occur if the knockout mice are kept on a restricted diet. Eating behavior is regulated by the hormone leptin. These fndings suggest that the leptin receptor might be located in the membrane of the primary cilia of the POMC neurons. 2007 2007 2007 2006 Conclusions Beginning with important electron microscopic studies and culminating in immunolocalization combined with molecular genetic technology, much has been learned about motile, sensory and primary cilia in mammals. Defects in building the primary cilium or mutations in ciliary membrane or axonemal proteins lead to ciliopathies, important human diseases. The cilium has moved to a prominent place in studies of embryogenesis and tissue differentiation and maintenance. There are hints that the fundamental cell biology of cilia will also be important in oncogenesis, aging diseases and human behavioral disorders. The strides of the past half century in understanding this organelle have been impressive, and the promise of discovery in the next half century is compelling.