Twist factor regulation of non-cardiomyocyte cell lineages in the developing heart

Nathan J VanDusen1, Anthony B Firulli

  • 1Riley Heart Research Center, Wells Center for Pediatric Research, Division of Pediatric Cardiology, Department of Medical and Molecular Genetics, Indiana Medical School, 1044 W. Walnut St., Indianapolis, IN 46202-5225, USA.

Insights

Twist-family transcription factors are crucial for heart development in non-cardiomyocyte lineages like the endocardium and epicardium. Understanding their roles is key to treating congenital heart defects and adult cardiac diseases.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Molecular Genetics

Background:

  • The heart comprises diverse cell types essential for proper cardiac morphogenesis.
  • Twist-family basic helix-loop-helix (bHLH) transcription factors regulate distinct cardiac and extra-cardiac lineages during cardiogenesis.
  • Non-cardiomyocyte contributions to heart development and disease are increasingly recognized.

Purpose of the Study:

  • To review the function of Twist-family bHLH proteins in extra-cardiac cell populations and the endocardium.
  • To focus on regulatory mechanisms, downstream targets, and expression profiles of these factors.
  • To highlight the importance of understanding these pathways for congenital and adult cardiac pathologies.

Main Methods:

  • Literature review of studies on Twist-family bHLH transcription factors.
  • Analysis of regulatory mechanisms, downstream targets, and expression patterns.
  • Synthesis of current knowledge on their roles in cardiac development and disease.

Main Results:

  • Twist-family bHLH factors exhibit distinct roles in cardiac neural crest (cNCC), epicardium, and endocardium.
  • These factors regulate key molecular pathways influencing cardiac development.
  • Dysfunction of these factors is linked to congenital heart diseases and adult pathologies like fibrosis.

Conclusions:

  • Elucidating Twist-family bHLH functions in non-cardiomyocytes is critical for understanding congenital heart disease.
  • Knowledge of these pathways is essential for developing improved treatments for adult cardiac conditions such as myocardial infarction and fibrosis.
  • This review provides a foundation for future research into Twist-family bHLH-mediated cardiac pathologies.

Related Concept Videos

Lineage Commitment01:21

Lineage Commitment

Commitment is the  process whereby stem cells:
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Forced Transdifferentiation01:28

Forced Transdifferentiation

Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial transdifferentiation occurs...
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...