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Related Concept Videos

Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...

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Related Experiment Video

Updated: May 12, 2026

Analysis of Cardiomyocyte Development using Immunofluorescence in Embryonic Mouse Heart
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PDGFRA is a conserved HAND2 effector during early cardiac development.

Yanli Xu1, Rupal Gehlot1, Samuel J Capon1

  • 1Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

Nature Cardiovascular Research
|December 10, 2024
PubMed
Summary
This summary is machine-generated.

The transcription factor HAND2 is crucial for heart development. DNA binding, not dimerization, is essential for HAND2 function in cardiogenesis, with PDGFR-alpha identified as a key downstream effector.

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • The transcription factor HAND2 plays a vital role in vertebrate organogenesis, particularly in heart development.
  • The precise molecular mechanisms underlying HAND2's function in cardiogenesis are not fully elucidated.

Purpose of the Study:

  • To investigate the functional domains of HAND2 required for cardiogenesis.
  • To identify critical downstream targets of HAND2 in embryonic cardiomyocytes.
  • To elucidate the role of PDGFR-alpha in HAND2-mediated heart development.

Main Methods:

  • Generation and analysis of various hand2 mutant alleles in zebrafish.
  • Transcriptome analysis of embryonic cardiomyocytes with altered HAND2 expression.
  • In vivo functional testing of candidate genes in zebrafish hand2 mutants.
  • Analysis of PDGFR-alpha expression in mouse embryonic stem cell-derived cardiac cells under different HAND2 conditions.

Main Results:

  • Dimerization-deficient HAND2 mutants exhibited a null phenotype, while DNA-binding-deficient mutants did not.
  • PDGFR-alpha was identified as a key effector gene, effectively rescuing myocardial migration defects in hand2 mutants.
  • A functional Hand2-binding region was identified in the zebrafish pdgfra locus, influencing its expression.
  • HAND2 modulates PDGFR-alpha expression in both zebrafish and mouse cardiac development models.

Conclusions:

  • HAND2's DNA-binding activity is essential for its function in cardiogenesis, whereas dimerization is dispensable.
  • PDGFR-alpha is a critical downstream target of HAND2, mediating myocardial migration during heart development.
  • This study provides significant insights into the molecular mechanisms governing HAND2's role in early vertebrate heart formation.