Dataset Information

Hdac4 Regulates the Proliferation of Neural Crest-Derived Osteoblasts During Murine Craniofacial Development.

ABSTRACT: Craniofacial development involves the regulation of a compendium of transcription factors, signaling molecules, and epigenetic regulators. Histone deacetylases (HDACs) are involved in the regulation of cell proliferation, differentiation, and homeostasis across a wide range of tissues, including the brain and the cardiovascular, muscular, and skeletal systems. However, the functional role of Hdac4 during craniofacial development remains unclear. In this study, we investigated the effects of knocking out Hdac4 on craniofacial skeletal development by conditionally disrupting the Hdac4 gene in cranial neural crest cells (CNCCs) using Cre-mediated recombination. Mice deficient for Hdac4 in CNCC-derived osteoblasts demonstrated a dramatic decrease in frontal bone formation. In vitro, pre-osteoblasts (MC3T3-E1 cells) lacking Hdac4 exhibited reduced proliferative activity in association with the dysregulation of cell cycle-related genes. These findings suggested that Hdac4 acts, at least in part, as a regulator of craniofacial skeletal development by positively regulating the proliferation of CNCC-derived osteoblasts.

SUBMITTER: Ha N

PROVIDER: S-EPMC8886889 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

<i>Hdac4</i> Regulates the Proliferation of Neural Crest-Derived Osteoblasts During Murine Craniofacial Development.

Ha Nayoung N Sun Jian J Bian Qian Q Wu Dandan D Wang Xudong X

Frontiers in physiology 20220215

Craniofacial development involves the regulation of a compendium of transcription factors, signaling molecules, and epigenetic regulators. Histone deacetylases (HDACs) are involved in the regulation of cell proliferation, differentiation, and homeostasis across a wide range of tissues, including the brain and the cardiovascular, muscular, and skeletal systems. However, the functional role of <i>Hdac4</i> during craniofacial development remains unclear. In this study, we investigated the effects ...[more]

PMID: 35242053

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Project description:Holoprosencephaly (HPE), the most common malformation of the human forebrain, is associated with defects of the craniofacial skeleton. ZIC2, a zinc-finger transcription factor, is strongly linked to HPE and to a characteristic set of dysmorphic facial features in humans. We have previously identified important functions for zebrafish Zic2 in the developing forebrain. Here, we demonstrate that ZIC2 orthologs zic2a and zic2b also regulate the forming zebrafish craniofacial skeleton, including the jaw and neurocranial cartilages, and use the zebrafish to study Zic2-regulated processes that may contribute to the complex etiology of HPE. Using temporally controlled Zic2a overexpression, we show that the developing craniofacial cartilages are sensitive to Zic2 elevation prior to 24hpf. This window of sensitivity overlaps the critical expansion and migration of the neural crest (NC) cells, which migrate from the developing neural tube to populate vertebrate craniofacial structures. We demonstrate that zic2b influences the induction of NC at the neural plate border, while both zic2a and zic2b regulate NC migratory onset and strongly contribute to chromatophore development. Both Zic2 depletion and early ectopic Zic2 expression cause moderate, incompletely penetrant mispatterning of the NC-derived jaw precursors at 24hpf, yet by 2dpf these changes in Zic2 expression result in profoundly mispatterned chondrogenic condensations. We attribute this discrepancy to an additional role for Zic2a and Zic2b in patterning the forebrain primordium, an important signaling source during craniofacial development. This hypothesis is supported by evidence that transplanted Zic2-deficient cells can contribute to craniofacial cartilages in a wild-type background. Collectively, these data suggest that zebrafish Zic2 plays a dual role during craniofacial development, contributing to two disparate aspects of craniofacial morphogenesis: (1) neural crest induction and migration, and (2) early patterning of tissues adjacent to craniofacial chondrogenic condensations.

Dataset Information

Hdac4 Regulates the Proliferation of Neural Crest-Derived Osteoblasts During Murine Craniofacial Development.

Publications

<i>Hdac4</i> Regulates the Proliferation of Neural Crest-Derived Osteoblasts During Murine Craniofacial Development.

Similar Datasets

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