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PMID:21734278

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Citation

Taylor, RW, Qi, JY, Talaga, AK, Ma, TP, Pan, L, Bartholomew, CR, Klionsky, DJ, Moens, CB and Gamse, JT (2011) Asymmetric inhibition of Ulk2 causes left-right differences in habenular neuropil formation. J. Neurosci. 31:9869-78

Abstract

Studies of the zebrafish epithalamus have provided recent insights into the development of left-right brain asymmetry, which is crucial to normal human brain function. The habenular nuclei of zebrafish are robustly asymmetric, with dense elaboration of neuropil only in the left lateral subnucleus. Because this feature is tightly correlated with asymmetric expression of K(+) channel tetramerization domain-containing proteins 12.1 and 12.2 (Kctd12.1/12.2), we screened for Kctd12.1-interacting proteins to identify molecular mechanisms leading to neuropil asymmetry, and uncovered a novel interaction between Kctd12.1 and Unc-51-like kinase 2 (Ulk2). We show here that knockdown of Ulk2 or overexpression of Kctd12 proteins reduces asymmetric neuropil elaboration. Conversely, overexpression of Ulk2 or mutation of kctd12 genes causes excess neuropil elaboration. We conclude that Ulk2 activity promotes neuropil elaboration while Kctd12 proteins limit Ulk2 activity asymmetrically. This work describes a regulatory mechanism for neuronal process extension that may be conserved in other developmental contexts in addition to the epithalamus.

Links

PubMed PMC3142468 Online version:10.1523/JNEUROSCI.0435-11.2011

Keywords

Alkylating Agents/pharmacology; Animals; Animals, Genetically Modified; Cation Transport Proteins/genetics; Cation Transport Proteins/metabolism; Ethylnitrosourea/pharmacology; Functional Laterality/drug effects; Functional Laterality/genetics; Functional Laterality/physiology; Gene Expression Regulation, Developmental/genetics; Gene Expression Regulation, Developmental/physiology; Green Fluorescent Proteins/genetics; Habenula/cytology; Habenula/drug effects; Habenula/growth & development; Habenula/injuries; Immunoprecipitation; Inhibition (Psychology); Larva; Mutation/genetics; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neuropil/drug effects; Neuropil/physiology; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins c-myc/metabolism; RNA, Messenger/metabolism; Tubulin/metabolism; Two-Hybrid System Techniques; Zebrafish; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A8KBL3

involved_in

GO:0021986: habenula development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110725-5

P

Seeded From UniProt

complete

DANRE:A8KBL3

involved_in

GO:0048814: regulation of dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110725-5

P

Seeded From UniProt

complete

DANRE:Q561T3

involved_in

GO:0021986: habenula development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110725-5

P

Seeded From UniProt

complete

DANRE:Q561T3

involved_in

GO:0048814: regulation of dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110725-5

P

Seeded From UniProt

complete

DANRE:Q804Q4

involved_in

GO:0021986: habenula development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110826-4

P

Seeded From UniProt

complete

DANRE:Q804Q4

involved_in

GO:0021986: habenula development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-110826-4,ZFIN:ZDB-MRPHLNO-110825-3

P

Seeded From UniProt

complete

DANRE:Q804Q4

involved_in

GO:0048814: regulation of dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110826-4

P

Seeded From UniProt

complete

DANRE:Q804Q4

involved_in

GO:0048814: regulation of dendrite morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-110826-4,ZFIN:ZDB-MRPHLNO-110825-3

P

Seeded From UniProt

complete

DANRE:X1WEA3

involved_in

GO:0021986: habenula development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110825-3

P

Seeded From UniProt

complete

DANRE:X1WEA3

involved_in

GO:0021986: habenula development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-110826-4,ZFIN:ZDB-MRPHLNO-110825-3

P

Seeded From UniProt

complete

DANRE:X1WEA3

involved_in

GO:0048814: regulation of dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-110825-3

P

Seeded From UniProt

complete

DANRE:X1WEA3

involved_in

GO:0048814: regulation of dendrite morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-110826-4,ZFIN:ZDB-MRPHLNO-110825-3

P

Seeded From UniProt

complete


See also

References

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