Roles of planar cell polarity pathways in the development of neutral tube defects

Neural tube defects (NTDs), arise when the neural tube, the embryonic precursor of the brain and spinal cord, fails to close during neurulation. Defects in neural tube closure are the second most common human birth defects, after congenital heart defects [1]. Recent birth prevalence estimates show that NTDs account for 0.5 per 1000 in the United States during 2001-2004, 1 to 1.5 per 1000 in Western Australia during 2001-2006, and 2.8 per 1000 in Iran during 1998-2005, while prevalence in Shanxi, a province in North China, reach to 19.9 per 1000 during 2002-2004 [2].The cranial region (anencephaly) or the low spine (open spina bifida and myelomeningocele) are most commonly affected [3]. NTDs affecting the brain are invariably lethal perinatally, whereas open spina bifida is compatible with postnatal survival but frequently results in serious handicap, because neurological impairment below the lesion leads to lack of sensation, inability to walk and incontinence [4].Neural tube closure is the result of neurulation, a process in which the neural plate bends upwards and eventually fuses to form the hollow tube that will become the brain and the spinal cord. The driving force of neural tube closure is provided and maintained by cells undergoing convergence and extension (CE) [5].Both fish (such as zebrafish) and amphibian (such as Xenopus) embryos require this process [6,7]. Neurulation is conserved between mammalian species [8] and can be conventionally divided into primary and secondary phases [9].In primary neurulation, the fusion occurs along the spine and culminates in final closure at the posterior neuropore. Closure is initiated at the hindbrain/cervical boundary (Closure 1) and then spreads bi-directionally into the hindbrain and along the spinal region. Separate closure initiation sites occur at the midbrain-forebrain boundary (Closure 2) and at the rostral extremity of the forebrain (Closure 3). However, Closure 2 found in mice may be absent from human neurulat