Disruption of Fuz in mouse embryos generates hypoplastic hindbrain development and reduced cranial nerve ganglia

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY
Carlo Donato Caiaffa, Yogeshwari S. Ambekar, Manmohan Singh, Ying Linda Lin, Bogdan Wlodarczyk, Salavat R. Aglyamov, Giuliano Scarcelli, Kirill V. Larin, Richard H. Finnell
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Abstract

Background

The brain and spinal cord formation is initiated in the earliest stages of mammalian pregnancy in a highly organized process known as neurulation. Environmental or genetic interferences can impair neurulation, resulting in clinically significant birth defects known collectively as neural tube defects. The Fuz gene encodes a subunit of the CPLANE complex, a macromolecular planar polarity effector required for ciliogenesis. Ablation of Fuz in mouse embryos results in exencephaly and spina bifida, including dysmorphic craniofacial structures due to defective cilia formation and impaired Sonic Hedgehog signaling.

Results

We demonstrate that knocking Fuz out during embryonic mouse development results in a hypoplastic hindbrain phenotype, displaying abnormal rhombomeres with reduced length and width. This phenotype is associated with persistent reduction of ventral neuroepithelial stiffness in a notochord adjacent area at the level of the rhombomere 5. The formation of cranial and paravertebral ganglia is also impaired in these embryos.

Conclusions

This study reveals that hypoplastic hindbrain development, identified by abnormal rhombomere morphology and persistent loss of ventral neuroepithelial stiffness, precedes exencephaly in Fuz ablated murine mutants, indicating that the gene Fuz has a critical function sustaining normal neural tube development and neuronal differentiation.

在小鼠胚胎中破坏 Fuz 会导致后脑发育不良和颅神经节减少。
背景:大脑和脊髓的形成始于哺乳动物怀孕的最初阶段,这一高度有序的过程被称为神经形成。环境或基因干扰会损害神经发育,导致临床上显著的出生缺陷,统称为神经管缺陷。Fuz 基因编码 CPLANE 复合物的一个亚基,CPLANE 复合物是纤毛形成所需的大分子平面极性效应器。在小鼠胚胎中敲除 Fuz 基因会导致无脑畸形和脊柱裂,包括由于纤毛形成缺陷和 Sonic Hedgehog 信号受损而导致的颅面结构畸形:结果:我们证明,在小鼠胚胎发育过程中敲除 Fuz 会导致后脑发育不良表型,表现出长度和宽度减少的异常菱形体。这种表型与菱形体5水平的脊索邻近区域腹侧神经上皮硬度持续降低有关。在这些胚胎中,颅神经节和椎旁神经节的形成也受到影响:本研究揭示了 Fuz 基因消减突变体后脑发育不良(表现为菱形体形态异常和腹侧神经上皮硬度持续丧失)先于颅外畸形的现象,表明 Fuz 基因具有维持正常神经管发育和神经元分化的关键功能。
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来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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