Forebrain patterning defects in Small eye mutant mice.
Forebrain patterning defects in Small eye mutant mice.
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发表时间：
1996-11
期刊：
影响因子：
4.6
通讯作者：
Anastassia Stoykova;R. Fritsch;C. Walther;Peter Gruss
中科院分区：
文献类型：
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作者：
Anastassia Stoykova;R. Fritsch;C. Walther;Peter Gruss
Pax6 是转录调节因子 Pax 基因家族的成员，在发育中的中枢神经系统、眼睛和鼻子中表现出受限的时空表达。 Pax6 突变导致人类、大鼠和小鼠的遗传性畸形。为了评估 Pax6 在前脑发育中的作用，我们详细研究了小鼠小眼/Pax6 突变体大脑。该分析揭示了 Pax6 特异性表达的前脑区域存在严重缺陷。沿着次级前脑背腹轴建立的一些表达边界被扭曲，并且几个腹侧结构和核的规范被废除。具体来说，下丘脑-端脑过渡区和腹侧丘脑的发育被扭曲。我们的详细分析包括比较野生型和突变型小眼 (Sey) 大脑中小鼠胚胎大脑发育过程中 Pax6、Dlx1 和其他几个基因的表达。对正常大脑发育的分析结果表明，Pax6 和 Dlx1 在 E12.5 dpc 处的受限表达涉及前脑内的域，这与前脑组织的前体模型的含义一致（L. Puelles 和 J. L. R. Rubenstein (1993) Trends Neurosci. 16, 472-479）。此外，我们发现 Pax6 和 Dlx1 表达的早期限制进入与不同前脑结构和细胞核的形成相关的假定组织发生区域。我们的结果是根据 Sey 大脑中粘附特性的变化进行讨论的，这些粘附特性可能控制特定前脑区域祖细胞的分离、组装和细胞迁移。
Pax6 is a member of the Pax gene family of transcriptional regulators that exhibits a restricted spatiotemporal expression in the developing central nervous system, eye and nose. Mutations in Pax6 are responsible for inherited malformations in man, rat and mouse. To evaluate the role of Pax6 in forebrain development, we studied in detail mouse Small eye/Pax6 mutant brains. This analysis revealed severe defects in forebrain regions where Pax6 is specifically expressed. The establishment of some expression boundaries along the dorsoventral axis of the secondary prosencephalon is distorted and the specification of several ventral structures and nuclei is abolished. Specifically, the development of the hypothalamo-telencephalic transition zone and the ventral thalamus is distorted. Our detailed analysis included a comparison of the expression of Pax6, Dlx1 and several other genes during embryonic mouse brain development in wild-type and in the mutant Small eye (Sey) brain. The results from the analysis of normal brain development show that the restricted expression of Pax6 and Dlx1 at E12.5 dpc respect domains within the forebrain, consistent with the implications of the prosomeric model for the organisation of the forebrain (L. Puelles and J. L. R. Rubenstein (1993) Trends Neurosci. 16, 472-479). Furthermore, we found an early restriction of Pax6 and Dlx1 expression into presumptive histogenetic fields that correlate with the formation of distinct forebrain structures and nuclei. Our results are discussed in light of changes in adhesive properties in the Sey brain that might control segregation, assembly and cell migration of progenitors of specific forebrain regions.