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PMID:24378336

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Citation

Huang, T and Krimm, RF (2014) BDNF and NT4 play interchangeable roles in gustatory development. Dev. Biol. 386:308-20

Abstract

A limited number of growth factors are capable of regulating numerous developmental processes, but how they accomplish this is unclear. The gustatory system is ideal for examining this issue because the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) have different developmental roles although both of them activate the same receptors, TrkB and p75. Here we first investigated whether the different roles of BDNF and NT4 are due to their differences in temporal and spatial expression patterns. Then, we asked whether or not these two neurotrophins exert their unique roles on the gustatory system by regulating different sets of downstream genes. By using Bdnf(Nt4/Nt4) mice, in which the coding region for BDNF is replaced with NT4, we examined whether the different functions of BDNF and NT4 are interchangeable during taste development. Our results demonstrated that NT4 could mediate most of the unique roles of BDNF during taste development. Specifically, caspase-3-mediated cell death, which was increased in the geniculate ganglion in Bdnf(-/-) mice, was rescued in Bdnf(Nt4/Nt4) mice. In BDNF knockout mice, tongue innervation was disrupted, and gustatory axons failed to reach their targets. However, disrupted innervation was rescued and target innervation is normal when NT4 replaced BDNF. Genome wide expression analyses revealed that BDNF and NT4 mutant mice exhibited different gene expression profiles in the gustatory (geniculate) ganglion. Compared to wild type, the expression of differentiation-, apoptosis- and axon guidance-related genes was changed in BDNF mutant mice, which is consistent with their different roles during taste development. However, replacement of BDNF by NT4 rescued these gene expression changes. These findings indicate that the functions of BDNF and NT4 in taste development are interchangeable. Spatial and temporal differences in BDNF and NT4 expression can regulate differential gene expression in vivo and determine their specific roles during development.

Links

PubMed PMC3950349 Online version:10.1016/j.ydbio.2013.12.031

Keywords

Analysis of Variance; Animals; Brain-Derived Neurotrophic Factor/genetics; Brain-Derived Neurotrophic Factor/metabolism; Carbocyanines; Gene Expression Profiling; Gene Expression Regulation, Developmental/genetics; Gene Expression Regulation, Developmental/physiology; Geniculate Ganglion/metabolism; Immunohistochemistry; Laser Capture Microdissection; Mice; Mice, Knockout; Microarray Analysis; Nerve Growth Factors/genetics; Nerve Growth Factors/metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Taste/physiology

Significance

Annotations

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

MOUSE:P2RX3

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NTF4

acts_upstream_of_or_within

GO:0061193: taste bud development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NTF4

acts_upstream_of_or_within

GO:0060548: negative regulation of cell death

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NTF4

acts_upstream_of_or_within

GO:0060384: innervation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TBB3

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BDNF

acts_upstream_of_or_within

GO:0060548: negative regulation of cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857136

P

Seeded From UniProt

complete

MOUSE:BDNF

acts_upstream_of_or_within

GO:0061193: taste bud development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857136

P

Seeded From UniProt

complete

MOUSE:CASP3

enables

GO:0097153: cysteine-type endopeptidase activity involved in apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

Notes

See also

References

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