Wnt genes define distinct boundaries in the developing human brain: Implications for human forebrain patterning

被引:58
作者
Abu-Khalil, A
Fu, L
Grove, EA
Zecevic, N
Geschwind, DH
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA
[2] Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA
[3] Univ Connecticut, Sch Med, Dept Neurosci, Farmington, CT 06030 USA
关键词
human fetal brain; WNT2b; WNT7b; DVL2; cerebral cortex; cortical hem; pineal gland; habenula;
D O I
10.1002/cne.20112
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Understanding the factors that govern human forebrain regionalization along the dorsal-ventral and left-right (L-R) axes is likely to be relevant to a wide variety of neurodevelopmental and neuropsychiatric conditions. Recent work in lower vertebrates has identified several critical signaling molecules involved in embryonic patterning along these axes. Among these are the Wingless-Int (WNT) proteins, involved in the formation of dorsal central nervous system (CNS) structures, as well as in visceral L-R asymmetry. We examined the expression of WNT2b and WNT7b in the human brain, because these genes have highly distinctive expression patterns in the embryonic mouse forebrain. In the human fetal telencephalon, WNT2b expression appears to define the cortical hem, a dorsal signaling center previously characterized in mouse, which is also confirmed by BMP7 expression. In diencephalon, WNT2b expression is restricted to medial dorsal structures, including the developing pineal gland and habenular nucleus, both implicated in CNS L-R asymmetry in lower organisms. At, 5 weeks gestation, WNT7b is expressed in cerebral cortical and diencephalic progenitor cells. As the cortical plate develops, WNT7b expression shifts, demarcating deep layer neurons of the neocortex and the hippocampal formation. Spatial and temporal expression patterns show startling similarity between human and mouse, suggesting that the developmental roles of these WNT genes may be highly conserved, despite the far greater size and complexity of the human forebrain. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:276 / 288
页数:13
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