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

Autor: Caiaffa, Carlo Donato, Ambekar, Yogeshwari S., Singh, Manmohan, Lin, Ying Linda, Wlodarczyk, Bogdan, Aglyamov, Salavat R., Scarcelli, Giuliano, Larin, Kirill V., Finnell, Richard H.
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Zdroj: Developmental Dynamics; Sep2024, Vol. 253 Issue 9, p846-858, 13p
Abstrakt: 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. Key Findings: Disruption of Fuz in mice embryos generates hypoplastic hindbrain and abnormal rhombomeres.Fuz mutant embryos exhibit persistent loss of ventral neural fold stiffness.Cranial and paravertebral ganglia development are reduced in Fuz ablated embryos.Fuz ablated embryos exhibit abnormal Sox10 positive neural crest migration. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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