2009 OSU Molecular Life Sciences
Interdisciplinary Graduate Programs Symposium
Poster abstracts
Abstract:
The vertebrate brain is a structure of remarkable complexity. However, the mechanisms by which the mature brain is sculpted during development remains incompletely understood. We have identified a member of the cadherin superfamily, protocadherin-19 (pcdh19), that play an essential role in early zebrafish brain morphogenesis. Pcdh-19 is a single pass transmembrane protein that exhibits a high degree of conservation among vertebrate species. Recent reports suggest that mutations in PCDH-19 in human results in an X-linked genetic disorder called Epilepsy and Mental Retardation limited to females (EFMR) (Dibbens et al., 2008; Depienne et al., 2009). In zebrafish, pcdh19 expression is seen as early as 6 hours post fertilization (hpf) and the expression continues throughout development. Pcdh-19 is expressed predominantly in the central nervous system. Using an anti-sense morpholino-based approach, we have found that Pcdh-19 knockdown in 24hpf embryos results in misfolded brain structures, especially at the midbrain-hindbrain boundary. Two-photon time lapse imaging of early neural development suggests that misfolding of the brain is preceded by defects in the convergence movements in the anterior neural plate. Understanding human neuropsychiatric disorders requires a detailed knowledge of their underlying molecular and cellular causes, including those that occur during development. Investigation of the brain morphogeneis in zebrafish can provide essential insights into both nervous system development and the developmental origins of brain defects.
References:
Dibbens, L. M., Tarpey, P. S. et al. (2008). X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat Genet 40, 776-81.
Depienne, C. et al. (2009). Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. Plos Genet 5, e1000381.
Keywords: zebrafish, Protocadherin, brain morphogenesis