PUBLICATION

Molecular genetics of maternally-controlled cell divisions

Authors

Abrams, E.W., Fuentes, R., Marlow, F.L., Kobayashi, M., Zhang, H., Lu, S., Kapp, L., Joseph, S.R., Kugath, A., Gupta, T., Lemon, V., Runke, G., Amodeo, A.A., Vastenhouw, N.L., Mullins, M.C.

ID

ZDB-PUB-200422-61

Date

2020

Source

PLoS Genetics 16: e1008652 (Journal)

Registered Authors

Abrams, Elliott, Gupta, Tripti, Joseph, Shai, Kapp, Lee, Kugath, Amy, Marlow, Florence, Mullins, Mary C., Runke, Greg, Vastenhouw, Nadine

Keywords

none

MeSH Terms

Maternal Inheritance/genetics*
Infertility, Male/genetics
Mutagenesis
Blastula/cytology
Blastula/embryology
Blastula/metabolism
Mutation*
Zebrafish/embryology*
Zebrafish/genetics*
Animals
Female
Cell Division/genetics*
Phenotype
Cytokinesis/genetics
Zebrafish Proteins/genetics
Male
Alleles
Body Patterning/genetics
Cell Nucleus
Embryonic Development/genetics*

(all 20)

PubMed

32267837 Full text @ PLoS Genet.

Abstract

Forward genetic screens remain at the forefront of biology as an unbiased approach for discovering and elucidating gene function at the organismal and molecular level. Past mutagenesis screens targeting maternal-effect genes identified a broad spectrum of phenotypes ranging from defects in oocyte development to embryonic patterning. However, earlier vertebrate screens did not reach saturation, anticipated classes of phenotypes were not uncovered, and technological limitations made it difficult to pinpoint the causal gene. In this study, we performed a chemically-induced maternal-effect mutagenesis screen in zebrafish and identified eight distinct mutants specifically affecting the cleavage stage of development and one cleavage stage mutant that is also male sterile. The cleavage-stage phenotypes fell into three separate classes: developmental arrest proximal to the mid blastula transition (MBT), irregular cleavage, and cytokinesis mutants. We mapped each mutation to narrow genetic intervals and determined the molecular basis for two of the developmental arrest mutants and a mutation causing male sterility and a maternal-effect mutant phenotype. One developmental arrest mutant gene encodes a maternal specific Stem Loop Binding Protein, which is required to maintain maternal histone levels. The other developmental arrest mutant encodes a maternal-specific subunit of the Minichromosome Maintenance Protein Complex, which is essential for maintaining normal chromosome integrity in the early blastomeres. Finally, we identify a hypomorphic allele of Polo-like kinase-1 (Plk-1), which results in a male sterile and maternal-effect phenotype. Collectively, these mutants expand our molecular-genetic understanding of the maternal regulation of early embryonic development in vertebrates.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
chrd	dun^{p15uzat/p15uzat}	standard conditions	Shield	Not Detected	gastrula cell	ISH	Fig. 6
chrd	WT	standard conditions	Shield		gastrula cell	ISH	Fig. 6
gsc	dun^{p15uzat/p15uzat}	standard conditions	Shield	Not Detected	shield	ISH	Fig. 6
gsc	WT	standard conditions	Shield		shield	ISH	Fig. 6
mcm3	WT	standard conditions	Adult		testis	RTPCR	Fig. 4
mcm3	WT	standard conditions	32-cell	Not Detected	whole organism	RTPCR	Fig. 4
mcm3	WT	standard conditions	75%-epiboly		whole organism	RTPCR	Fig. 4
mcm3	WT	standard conditions	Prim-5		whole organism	RTPCR	Fig. 4
mcm3	WT	standard conditions	1k-cell		whole organism	RTPCR	Fig. 4
mcm3	WT	standard conditions	1-cell	Not Detected	whole organism	RTPCR	Fig. 4

1 - 10 of 22

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
bmb^{p22atuz/p22atuz}	standard conditions	128-cell	developmental process arrested, abnormal	Fig. 1
cld^{p40atuza/p40atuza}	standard conditions	16-cell	embryonic cleavage asynchronous, abnormal	Fig. 1
cld^{p40atuza/p40atuza}	standard conditions	4-cell	embryonic cleavage asynchronous, abnormal	Fig. 1
cld^{p40atuza/p40atuza}	standard conditions	16-cell	whole organism cell opaque, abnormal	Fig. 1
cld^{p40atuza/p40atuza}	standard conditions	4-cell	whole organism cell opaque, abnormal	Fig. 1
cld^{p40atuza/p40atuza}	standard conditions	Sphere	embryonic cleavage asynchronous, abnormal	Fig. 1
cld^{p40atuza/p40atuza}	standard conditions	Sphere	whole organism cell opaque, abnormal	Fig. 1
dsy^{p86batl/p86batl}	standard conditions	8-cell	embryonic cleavage asynchronous, abnormal	Fig. 1
dsy^{p86batl/p86batl}	standard conditions	2-cell	embryonic cleavage asynchronous, abnormal	Fig. 1
dsy^{p86batl/p86batl}	standard conditions	4-cell	embryonic cleavage asynchronous, abnormal	Fig. 1

1 - 10 of 29

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
p01aiue		Unknown	birc5b
p04anua		Unknown	unm_p04anua
p5Tg	Tg(actb2:plk1,myl7:EGFP)	Transgenic Insertion
p09ajug		Point Mutation	plk1
p09batl		Unknown	mxp
p10umal		Point Mutation	mcm3l
p15uzat		Unknown	dun
p18ad		Unknown	slbp2
p22atuz		Point Mutation	bmb
p40atuza		Unknown	cld

1 - 10 of 14

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
bmb^{p22atuz/p22atuz}
cld^{p40atuza/p40atuza}
dsy^{p86batl/p86batl}
dun^{p15uzat/p15uzat}
mcm3l^{p10umal/p10umal}
mxp^{p09batl/p09batl}
plk1^{p09ajug/p09ajug}
slbp2^p18ad/p18ad
WT

Antibodies

Name	Type	Isotypes	Host Organism
Ab1-h2b	polyclonal	IgG	Rabbit
Ab2-tuba	monoclonal	IgG1	Mouse
Ab3-h4	polyclonal	IgG	Rabbit
Ab15-h3	polyclonal	IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Abrams et al., 2020 ZDB-PUB-200422-61 PMID:32267837

Molecular genetics of maternally-controlled cell divisions

Abrams et al., 2020

ZDB-PUB-200422-61
PMID:32267837