Disruption of Fuz in Mouse Embryos Generates Hypoplastic Hindbrain Development and Reduced Cranial Nerve Ganglia

Authors

Carlo Donato Caiaffa
Yogeshwari S Ambekar
Manmohan Singh
Ying Linda Lin
Bogdan Wlodarczyk
Salavat R Aglyamov
Giuliano Scarcelli
Kirill V Larin
Richard H Finnell

Language

English

Publication Date

9-1-2024

Journal

Developmental Dynamics

DOI

10.1002/dvdy.702

PMID

38501709

PMCID

PMC11411014

PubMedCentral® Posted Date

9-1-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Animals, Rhombencephalon, Mice, Cranial Nerves, Mice, Knockout, Female, Embryo, Mammalian, Ganglia, Pregnancy, Neural tube defects, Fuz, optical coherence tomography, Brillouin light scattering, immunohistochemistry, neuroepithelial stiffness, abnormal rhombomeres, hypoplastic hindbrain

Published Open-Access

yes

Recommended Citation

Caiaffa, Carlo Donato; Ambekar, Yogeshwari S; Singh, Manmohan; et al., "Disruption of Fuz in Mouse Embryos Generates Hypoplastic Hindbrain Development and Reduced Cranial Nerve Ganglia" (2024). Faculty and Staff Publications. 4856.
https://digitalcommons.library.tmc.edu/baylor_docs/4856