Aberrant forebrain signaling during early development underlies the generation of holoprosencephaly and coloboma

作者：Gongal Patricia A; French Curtis R; Waskiewicz Andrew J^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2011, 1812(3): 390-401.

DOI：10.1016/j.bbadis.2010.09.005

• Holoprosencephaly
• Coloboma
• Sonic hedgehog
• Gdf6
• Retinoic acid
• Retina

In this review, we highlight recent literature concerning the signaling mechanisms underlying the development of two neural birth defects, holoprosencephaly and coloboma. Holoprosencephaly, the most common forebrain defect, occurs when the cerebral hemispheres fail to separate and is typically associated with mispatterning of embryonic midline tissue. Coloboma results when the choroid fissure in the eye fails to close. It is clear that Sonic hedgehog (Shh) signaling regulates both forebrain and eye development, with defects in Shh, or components of the Shh signaling cascade leading to the generation of both birth defects. In addition, other intercellular signaling pathways are known factors in the incidence of holoprosencephaly and coloboma. This review will outline recent advances in our understanding of forebrain and eye embryonic pattern formation, with a focus on zebrafish studies of Shh and retinoic acid pathways. Given the clear overlap in the mechanisms that generate both diseases, we propose that holoprosencephaly and coloboma can represent mild and severe aspects of single phenotypic spectrum resulting from aberrant forebrain development. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases.

• 出版日期2011-3