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Distinct and redundant roles for zebrafish her genes during osteoblast differentiation and craniofacial patterning.

ABSTRACT: Distinct and redundant roles for zebrafish her genes during osteoblast differentiation and craniofacial patterning.

PROVIDER: PRJNA908775 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22528405_1.fastq.gz	Fastqsanger.gz
	SRR22528405_2.fastq.gz	Fastqsanger.gz

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Distinct and redundant roles for zebrafish her genes during osteoblast differentiation and craniofacial patterning.

Project description:The Notch pathway is a cell-cell communication system which is critical for many developmental processes, including craniofacial development. Notch receptor activation induces expression of several well-known canonical targets including those encoded by the hes and her genes in mammals and zebrafish, respectively. The function of these genes, individually and in combination, during craniofacial development is not well understood. Here, we investigated zebrafish her9 and her6 gene function during craniofacial development. We found that her9 is required for osteoblasts to efficiently mineralize bone, while cartilage is largely unaffected. Strikingly, gene expression studies in her9 mutants indicate that although progenitor cells differentiate into osteoblasts at the appropriate time and place, they fail to efficiently lay down mineralized matrix. This mineralization role of her9 is likely independent of Notch activation. In contrast, her9 also functions redundantly with her6 downstream of Jagged1b-induced Notch activation during dorsoventral craniofacial patterning. These studies disentangle distinct and redundant her gene functions during craniofacial development, including an unexpected, Notch independent, requirement during bone mineralization

2022-12-12 | GSE220081 | GEO

Distinct and redundant roles for zebrafish <i>her</i> genes during mineralization and craniofacial patterning.

Project description:The Notch pathway is a cell-cell communication system which is critical for many developmental processes, including craniofacial development. Notch receptor activation induces expression of several well-known canonical targets including those encoded by the hes and her genes in mammals and zebrafish, respectively. The function of these genes, individually and in combination, during craniofacial development is not well understood. Here, we used zebrafish genetics to investigate her9 and her6 gene function during craniofacial development. We found that her9 is required for osteoblasts to efficiently mineralize bone, while cartilage is largely unaffected. Strikingly, gene expression studies in her9 mutants indicate that although progenitor cells differentiate into osteoblasts at the appropriate time and place, they fail to efficiently lay down mineralized matrix. This mineralization role of her9 is likely independent of Notch activation. In contrast, her9 also functions redundantly with her6 downstream of Jagged1b-induced Notch activation during dorsoventral craniofacial patterning. These studies disentangle distinct and redundant her gene functions during craniofacial development, including an unexpected, Notch independent, requirement during bone mineralization.

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Project description:Wnt signaling plays a fundamental role in the initial patterning and development of the embryo, including in the regulation of convergent extension during gastrulation and the establishment of the dorsal axis. Further, Wnt signaling is a crucial regulator of craniofacial morphogenesis. The relationship between early embryo patterning and craniofacial outcomes warrants further study. The adapter proteins Dact1 and Dact2 modulate the Wnt signaling pathway through binding to Disheveled, however, the distinct roles of Dact1 and Dact2 during embryogenesis remain to be fully elucidated. In this study, we investigated the spatiotemporal gene expression patterns of dact1 and dact2 during zebrafish embryogenesis, revealing both shared and unique domains of expression. We found that both dact1 and dact2 contribute to axis extension, with compound mutants exhibiting a similar convergent extension defect and craniofacial phenotype to the wnt11f2/slb mutant. Utilizing single-cell RNAseq and gpc4-/- zebrafish, a convergent extension mutant with an opposite craniofacial phenotype, we identified dact1/2 specific roles during early development. Using this subtractive approach, we discovered a novel role for dact1/2 in regulating the mRNA expression of the classical calpain, capn8, suggesting a previously unappreciated role of calcium-dependent proteolysis during embryogenesis. Taken together, our findings highlight the distinct and overlapping roles of dact1 and dact2 in embryonic craniofacial development, providing new insights into the multifaceted regulation of Wnt signaling.

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