PUBLICATION

Connexin43 (GJA1) is required in the population of dividing cells during fin regeneration

Authors

Hoptak-Solga, A.D., Nielsen, S., Jain, I., Thummel, R., Hyde, D.R., and Iovine, M.K.

ID

ZDB-PUB-080415-14

Date

2008

Source

Developmental Biology 317(2): 541-548 (Journal)

Registered Authors

Hyde, David R., Iovine, M. Kathryn, Thummel, Ryan

Keywords

Bone growth, short fin, Regeneration, Zebrafish, Cell proliferation, Cx43, GJIC

MeSH Terms

Animal Structures/physiology*
Zebrafish/genetics*
Zebrafish/physiology
Gap Junctions/physiology*
Cell Proliferation
Animals
Cell Communication/physiology*
Mutation/genetics
Cryoultramicrotomy
In Situ Hybridization
Connexin 43/genetics
Connexin 43/metabolism*
Regeneration/physiology*
Electroporation
Immunoblotting

(all 15)

PubMed

18406403 Full text @ Dev. Biol.

Abstract

In zebrafish, mutations in the gap junction gene connexin43 lead to short bony fin ray segments that give rise to the short fin phenotype. The sof(b123) mutant exhibits fins that are half the length of wild-type fins and have reduced levels of cx43 mRNA. We find that sof(b123) regenerating fins exhibit reduced levels of cell proliferation. Interestingly, the number of dividing cells per unit length of fin growth is similar between wild-type and mutant fins, suggesting that the number of cells that enter the cell cycle is specifically affected in sof(b123). Expression of cx43 is identified in mitotic cells, which further suggests that Cx43 may contribute to establishing or maintaining the population of dividing cells. Indeed, missense alleles exhibiting high or low levels of gap junctional communication reveal a correlation between defects in direct cell-cell communication, cell proliferation, and segment length. Finally, targeted gene knockdown of cx43 in adult regenerating fins recapitulates the sof(b123) phenotype, revealing that the loss of Cx43 is sufficient to reduce both cell proliferation and segment length. We hypothesize that the level of gap junctional intercellular communication among dividing cells regulates the level of cell proliferation and ultimately regulates bone growth.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Antibody	Fish	Conditions	Stage	Anatomy	Assay	Figure
gja1b	ab1-cx43	C32	standard conditions	Adult	joint	IHC	Fig. 4
gja1b	ab1-cx43	C32	standard conditions	Adult	mesenchyme	IHC	Fig. 5
gja1b		C32	standard conditions	Adult	mesenchyme	ISH	Fig. 2
gja1b	ab1-cx43	C32	control	Adult	mesenchyme	IHC	Fig. 5
gja1b	ab1-cx43	C32	standard conditions	Adult	mesenchyme	IHC	Fig. 4
gja1b	ab1-cx43	C32	standard conditions	Adult	regenerating fin	IHC	Fig. 4
gja1b	ab1-cx43	C32	standard conditions	Adult	regenerating fin	WB	Fig. 4
gja1b	ab1-cx43	C32	standard conditions	Adult	regenerating fin	IHC	Fig. 5
gja1b		C32	standard conditions	Adult	regenerating fin	ISH	Fig. 2
gja1b	ab1-cx43	C32	control	Adult	regenerating fin	IHC	Fig. 5

1 - 10 of 22

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
C32 + MO1-gja1b	standard conditions	Adult	cell population proliferation disrupted, abnormal	Fig. 6
C32 + MO1-gja1b	standard conditions	Adult	fin regeneration hypotrophic growth, abnormal	Fig. 6
C32 + MO1-gja1b	standard conditions	Adult	regenerating fin decreased length, abnormal	Fig. 6
C32 + MO2-gja1b	standard conditions	Adult	cell population proliferation disrupted, abnormal	Fig. 6
C32 + MO2-gja1b	standard conditions	Adult	fin regeneration hypotrophic growth, abnormal	Fig. 6
C32 + MO2-gja1b	standard conditions	Adult	regenerating fin decreased length, abnormal	Fig. 6
gja1b^b123/b123 (C32)	standard conditions	Adult	cell population proliferation disrupted, abnormal	Fig. 1
gja1b^b123/b123 (C32)	standard conditions	Adult	cell population proliferation disrupted, abnormal	Fig. 4
gja1b^b123/b123 (C32)	standard conditions	Adult	fin regeneration disrupted, abnormal	Fig. 4
gja1b^b123/b123 (C32)	standard conditions	Adult	fin regeneration hypotrophic growth, abnormal	Fig. 1

1 - 10 of 14

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Mutations / Transgenics

Allele	Type	Affected Genomic Region
b123	Unknown	gja1b
j7e1	Point Mutation	gja1b
j7e2	Point Mutation	gja1b
j7e3	Point Mutation	gja1b

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
gja1b	MO1-gja1b	MRPHLNO
gja1b	MO2-gja1b	MRPHLNO

Fish

Fish
C32
C32 + MO1-gja1b
C32 + MO2-gja1b
gja1b^b123/b123 (C32)
gja1b^j7e1/j7e1 (C32)
gja1b^j7e2/j7e2 (C32)
gja1b^j7e3/j7e3 (C32)

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-cx43	polyclonal	gja1b		Rabbit
Ab1-h3	polyclonal		IgG	Rabbit
Ab2-tuba	monoclonal		IgG1	Mouse

Orthology

Engineered Foreign Genes

Mapping

Hoptak-Solga et al., 2008 ZDB-PUB-080415-14 PMID:18406403

Connexin43 (GJA1) is required in the population of dividing cells during fin regeneration

Hoptak-Solga et al., 2008

ZDB-PUB-080415-14
PMID:18406403