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PMID:17531968

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Citation

Morikawa, Y, D'Autréaux, F, Gershon, MD and Cserjesi, P (2007) Hand2 determines the noradrenergic phenotype in the mouse sympathetic nervous system. Dev. Biol. 307:114-26

Abstract

The basic helix-loop-helix (bHLH) transcription factor Hand2 has been shown to play a role in the development of the mammalian sympathetic nervous system (SNS); however, its precise role could not be uncovered because Hand2 is required for early embryonic survival. We therefore generated a conditional Hand2 knockout mouse line by excising Hand2 in Wnt1-Cre-expressing neural crest-derived cells. These mice die at 12.5 dpc with embryos showing severe cardiovascular and facial defects. Crest-derived cells, however, populate sites of SNS development and proliferate normally. Sympathetic precursors differentiate into neurons and express the pan-neuronal markers, beta3-tubulin (Tuj1) and Hu showing that Hand2 is not essential for SNS neuronal differentiation. To determine whether Hand2 regulates noradrenergic differentiation, the levels of the norepinephrine biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) was examined. Both enzymes were dramatically reduced in mutant embryos suggesting that the primary role of Hand2 in the SNS is determination of neuronal phenotype. Loss of Hand2 did not affect the expression of other members of the transcriptional circuit regulating SNS development, including Phox2a/b, Mash1 and Gata2/3; however, Hand2 was required for Hand1 expression. Our data suggest that the major role of Hand2 during SNS development is to permit sympathetic neurons to acquire a catecholaminergic phenotype.

Links

PubMed PMC1952239 Online version:10.1016/j.ydbio.2007.04.027

Keywords

Animals; Basic Helix-Loop-Helix Transcription Factors/deficiency; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/physiology; Catecholamines; Cell Differentiation; Cell Proliferation; Embryo, Mammalian; Mice; Mice, Knockout; Neural Crest/cytology; Neurons/cytology; Norepinephrine; Phenotype; Sympathetic Nervous System/growth & development; Transcription Factors

Significance

Annotations

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

MOUSE:HAND2

acts_upstream_of_or_within

GO:0060021: roof of mouth development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3715149

P

Seeded From UniProt

complete

MOUSE:HAND2

acts_upstream_of_or_within

GO:0043586: tongue development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3715149

P

Seeded From UniProt

complete

MOUSE:HAND2

acts_upstream_of_or_within

GO:1903929: primary palate development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3715149

P

Seeded From UniProt

complete

MOUSE:HAND2

acts_upstream_of_or_within

GO:0001967: suckling behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3715149

P

Seeded From UniProt

complete


See also

References

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