Abstract
During neurulation, vertebrate embryos form a neural tube (NT), the rudiment of the central nervous system. In mammals and birds, a key step in cranial NT morphogenesis is dorsolateral hinge-point (DLHP) bending, which requires an apical actomyosin network. The mechanism of DLHP formation is poorly understood, although several essential genes have been identified, among them Zic2, which encodes a zinc-finger transcription factor. We found that DLHP formation in the zebrafish midbrain also requires actomyosin and Zic function. Given this conservation, we used the zebrafish to study how genes encoding Zic proteins regulate DLHP formation. We demonstrate that the ventral zic2a expression border predicts DLHP position. Using morpholino (MO) knockdown, we show zic2a and zic5 are required for apical F-actin and active myosin II localization and junction integrity. Furthermore, myosin II activity can function upstream of junction integrity during DLHP formation, and canonical Wnt signaling, an activator of zic gene transcription, is necessary for apical active myosin II localization, junction integrity and DLHP formation. We conclude that zic genes act downstream of Wnt signaling to control cytoskeletal organization, and possibly adhesion, during neurulation. This study identifies zic2a and zic5 as crucial players in the genetic network linking patterned gene expression to morphogenetic changes during neurulation, and strengthens the utility of the zebrafish midbrain as a NT morphogenesis model.
Highlights
Neurulation is the major morphogenetic process that shapes the vertebrate central nervous system (CNS, the future brain and spinal cord) during embryonic development
We found that dorsolateral hinge-point (DLHP) formation in the zebrafish midbrain requires actomyosin and Zic function
We demonstrate that the ventral zic2a expression border predicts DLHP position
Summary
Neurulation is the major morphogenetic process that shapes the vertebrate central nervous system (CNS, the future brain and spinal cord) during embryonic development. The cranial neural plate thickens at the lateral edges to form neural folds. These folds elevate toward the dorsal surface and bend inward toward the dorsal midline at dorsolateral hinge points (DLHPs). A teleost, neural plate cells elongate and converge to form a neural keel, and intercalate to form a dorsally closed rod (Hong and Brewster, 2006). This solid rod subsequently forms DLHPs and cavitates to make a tube
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