PUBLICATION

Integrated K+ channel and K+Cl- cotransporter function are required for the coordination of size and proportion during development

Authors

Lanni, J.S., Peal, D., Ekstrom, L., Chen, H., Stanclift, C., Bowen, M.E., Mercado, A., Gamba, G., Kahle, K.T., Harris, M.P.

ID

ZDB-PUB-190902-23

Date

2019

Source

Developmental Biology 456(2): 164-178 (Journal)

Registered Authors

Harris, Matthew

Keywords

none

MeSH Terms

Potassium Channels, Voltage-Gated/metabolism
Male
Signal Transduction/genetics
Animal Fins/growth & development*
Animal Fins/metabolism
Potassium Chloride/metabolism
Female
Regeneration
Zebrafish/genetics
Organ Size/physiology*
Cell Size
Symporters/metabolism*
Animals
Mutation/genetics
Zebrafish Proteins/genetics

PubMed

31472116 Full text @ Dev. Biol.

Abstract

The coordination of growth during development establishes proportionality within and among the different anatomic structures of organisms. Innate memory of this proportionality is preserved, as shown in the ability of regenerating structures to return to their original size. Although the regulation of this coordination is incompletely understood, mutant analyses of zebrafish with long-finned phenotypes have uncovered important roles for bioelectric signaling in modulating growth and size of the fins and barbs. To date, long-finned mutants identified are caused by hypermorphic mutations, leaving unresolved whether such signaling is required for normal development. We isolated a new zebrafish mutant, schleier, with proportional overgrowth phenotypes caused by a missense mutation and loss of function in the K⁺-Cl^- cotransporter Kcc4a. Creation of dominant negative Kcc4a in wild-type fish leads to loss of growth restriction in fins and barbs, supporting a requirement for Kcc4a in regulation of proportion. Epistasis experiments suggest that Kcc4a and the two-pore potassium channel Kcnk5b both contribute to a common bioelectrical signaling response in the fin. These data suggest that an integrated bioelectric signaling pathway is required for the coordination of size and proportion during development.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
slc12a7a^dmh39/+	standard conditions	Adult	caudal fin mesenchyme	ISH	Fig. 4
slc12a7a^dmh39/+	standard conditions	Adult	caudal fin	RTPCR	Fig. 4
slc12a7a^dmh39/+	standard conditions	Adult	epidermis mesenchyme	ISH	Fig. 4
WT	standard conditions	Adult	caudal fin mesenchyme	ISH	Fig. 4
WT	standard conditions	Adult	caudal fin	RTPCR	Fig. 4
WT	standard conditions	Adult	epidermis mesenchyme	ISH	Fig. 4
slc12a7a^dmh39/+	standard conditions	Adult	caudal fin	ISH	Fig. 4
slc12a7a^dmh39/+	standard conditions	Adult	caudal fin	RTPCR	Fig. 4
WT	standard conditions	Adult	caudal fin	ISH	Fig. 4
WT	standard conditions	Adult	caudal fin	RTPCR	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
slc12a7a^dmh39/+	standard conditions	Adult	barbel increased length, abnormal	Fig. 1
slc12a7a^dmh39/+	standard conditions	Adult	caudal fin slc12a7b expression decreased amount, abnormal	Fig. 4
slc12a7a^dmh39/+	standard conditions	Adult	caudal fin epidermis Ab1-slc12a7a labeling decreased amount, abnormal	Fig. 4
slc12a7a^dmh39/+	standard conditions	Adult	caudal fin lepidotrichium increased length, abnormal	Fig. 1
slc12a7a^dmh39/+	standard conditions	Adult	caudal fin mesenchyme Ab1-slc12a7a labeling decreased amount, abnormal	Fig. 4
slc12a7a^dmh39/+	standard conditions	Adult	fin increased length, abnormal	Fig. 1
slc12a7a^dmh39/+	standard conditions	Adult	lepidotrichium fractured, abnormal	Fig. 1
slc12a7a^dmh39/+	standard conditions	Adult	lepidotrichium increased thickness, abnormal	Fig. 1
slc12a7a^dmh39/+	standard conditions	Adult	lepidotrichium morphology, abnormal	Fig. 1
slc12a7a^dmh39/+; y1Tg	standard conditions	Adult	caudal fin accumulation blood, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
dmh39		Point Mutation	slc12a7a
dt2		Unknown	lof
y1Tg	Tg(fli1:EGFP)	Transgenic Insertion
zf3270		Small Deletion	slc12a7a
zf3271		Small Deletion	slc12a7a

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Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Lanni et al., 2019 ZDB-PUB-190902-23 PMID:31472116

Integrated K+ channel and K+Cl- cotransporter function are required for the coordination of size and proportion during development

Lanni et al., 2019

ZDB-PUB-190902-23
PMID:31472116