**5. Acknowledgement**

The authors warmly thank Thelma Coyle for correcting de English language of the chapter.

### **6. References**


their phantom limb. Some results in the literature suggest that the sending of motor commands is necessary in order to "perform" voluntary phantom limb movements. These motor commands, as they cannot arrive on the muscles of the lost limb, arrive on the muscles of the stump instead. Indeed, during voluntary phantom limb movements, the EMG pattern found on the stump muscles correspond to neither the EMG patterns for real movements of the stump, nor to the EMG patterns found on the corresponding muscles of the intact arm during imitation of the phantom limb movements (Reilly et al., 2006; Gagné et al., 2009). This strongly suggests that specific motor commands are sent from M1 when "executing" a specific phantom limb movement. Moreover, when the hand area of M1 in an amputated patient is stimulated with TMS, a phantom limb movement is evoked (Mercier et al., 2006). So, there exists a reorganization of the primary somatosensory and motor areas, leading to new relations between body parts and neuronal populations, where motor

There seems to exist a relation between the degree of cortical reorganization and the degree of phantom limb pain. Lotze and colleagues (2001), in a fMRI study, reported that patients without phantom limb pain showed significantly less reorganization of the primary sensorimotor areas than patients with phantom limb pain. This raises the question whether

Currently, it is not known what exactly underlies the appearance of phantom limb sensations such as movements or pain, but it seems likely that it is, at least partly, related to the complex cortical reorganization following amputation. The search for answers to questions such as "What causes phantom limb pain and how can we avoid it?", "Why are phantom limb movements slow and effortful?", and "Can we use phantom limb movements to increase control of prostheses?", must take into account that the primary cortical areas are an integral part of a cortical network underlying cognitive (motor) functioning, and the secondary motor areas can have an executive function. With respect to this latter point, a possible reorganization of the secondary motor areas following amputation has not yet been

The authors warmly thank Thelma Coyle for correcting de English language of the chapter.

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**8** 

**Ciliopathies: Primary Cilia** 

**in Mammalian Development** 

Carmen Carrascosa Romero1, José Luis Guerrero Solano2

**1. Introduction** 

clear function.

likenesses" to life [4].

**1.1 Ciliopathies, an emerging class of human genetic diseases** 

The physiological role of motile cilia or flagella in cell locomotion, sexual reproduction and fluid movements is well known. In 1898, the Swiss anatomist KW Zimmerman first described cilia on the surface of mammalian cells, for which he suggested a sensory role. His findings were largely ignored until the late 1960s, when Wheatley, using the electron microscope, stumbled upon a properly sized bubble in his histological preparation, verifying it as the cilium described by Zimmerman 63 years earlier[1]. Although it became known that all cells, from green alga Chlamydomonas to human cells – especially kidney cells– possessed a nonmotile cilium, it was initially considered a vestigial structure with no

Recent discoveries have assigned novel functions to primary (nonmotile) cilia, ranging from mechanosensory in maintaining cellular homeostasis, to participation in signal transduction pathways that regulate intracellular Ca2+levels. Furthermore, the cilium is now emerging as an essential organelle in morphogenesis, important to key developmental pathways such as Sonic Hedgehog (Shh) and Wnt (planar cell polarity (PCP) pathways). The function of nodal cilia, for example, is vital for breaking early embryonic symmetry, Shh signaling is important for tissue morphogenesis and successful Wnt signaling for organ growth and differentiation. Defects in cilia formation or function have profound effects on anatomical development and the physiology of multiple organ systems such as death of photoreceptors, kidney tubule cysts, extra limb digits and brain malformation [2, 3]. Alterations in ciliary function also play a role in specific organ diseases (polycystic kidney disease, pigmentosa retinitis...) and pleiotropic phenotypes (Bardet-Bield Syndrome, Alstrom S., Meckel-Gruber S., Oro-Facio-Digital S...), until recently of unknown origin. Our greater knowledge of genetics and the recognized role of cilium in morphogenetic signaling pathways, especially in neurogenesis, bring Bronowski's phrase "All science is the search for unity in hidden

*3Neuropsychopharmacology Units, Albacete General Hospital* 

**and Signaling Pathways** 

and Carlos De Cabo De La Vega3

*1Neuropediatrics, 2Neurophsyology and* 

*Spain* 

