Journal
DEVELOPMENTAL BIOLOGY
Volume 334, Issue 1, Pages 72-83Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2009.07.008
Keywords
Zebrafish; Protocadherin; Brain morphogenesis; Neurulation; Convergence
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Funding
- NIH-NCRR [RR12546]
- Burroughs Wellcome Fund Career Award in the Biomedical Sciences
- NSF [IOS-0920357]
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [0920357] Funding Source: National Science Foundation
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One of the earliest stages of brain morphogenesis is the establishment of the neural tube during neurulation. While some of the cellular mechanisms responsible for neurulation have been described in a number of vertebrate species, the underlying molecular processes are not fully understood. We have identified the zebrafish homolog of protocadherin-19, a member of the cadherin superfamily, which is expressed in the anterior neural plate and is required for brain morphogenesis. Interference with Protocadherin-19 function with antisense morpholino oligonucleotides leads to a severe disruption in early brain morphogenesis. Despite these pronounced effects on neurulation, axial patterning of the neural tube appears normal, as assessed by in situ hybridization for otx2, pax2.1 and krox20. Characterization of embryos early in development by in vivo 2-photon timelapse microscopy reveals that the observed disruption of morphogenesis results from an arrest of cell convergence in the anterior neural plate. These results provide the first functional data for protocadherin-19, demonstrating an essential role in early brain development. (C) 2009 Elsevier Inc. All rights reserved.
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