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Transcripts encoding HAND genes are differentially expressed and regulated by BMP4 and GDNF in developing avian gut
1Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo, 3000 Arlington Ave., OH 43614, USA.
Gene Expression
|November 27, 2002
Summary
Basic helix-loop-helix transcription factors HAND2 and HAND1 are key in gut development. BMP4 and GDNF differentially regulate HAND2 and HAND1 expression in neural crest cells and gut tissues, impacting enteric neuron development.
Area of Science:
- Developmental biology
- Neuroscience
- Genetics
Background:
- Neural crest-derived cells form enteric neurons, guided by developmental cues.
- Basic helix-loop-helix transcription factors HAND2 and HAND1 are present in the gastrointestinal tract.
- The specific cell types and inducing factors for HAND1/HAND2 expression in the gut remain unknown.
Purpose of the Study:
- To identify the cell types expressing HAND1 and HAND2 in the developing gut.
- To investigate the roles of gut-derived factors, specifically BMP4 and GDNF, in regulating HAND1 and HAND2 expression.
- To elucidate the differential regulation of HAND1 and HAND2 by growth factors in neural crest development.
Main Methods:
- In situ hybridization combined with cell type-specific immunostaining.
- Coculture of neural crest-derived cells with gut explants.
- Treatment of cells with Bone Morphogenetic Protein 4 (BMP4) and Glial cell line-Derived Neurotrophic Factor (GDNF).
Main Results:
- HAND2 transcripts are found in enteric neurons throughout the gut, while HAND1 transcripts are restricted to the small intestine and colon.
- BMP4 significantly increased HAND2 expression in all gut segments and induced HAND1 expression in non-neural crest cells of the esophagus and gizzard.
- GDNF showed a modest increase in HAND2 expression in specific gut-derived neural crest cells but had no effect on HAND1 expression.
Conclusions:
- HAND2 plays a role in the development of enteric neurons.
- BMP4 and GDNF exhibit differential regulation of HAND2 and HAND1 gene expression.
- Understanding these regulatory mechanisms is crucial for gastrointestinal development and potential therapeutic interventions.
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Transcription
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Transcription
Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in correctly synthesizing messenger RNA (mRNA). Transcriptional regulation is responsible for the differentiation of different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
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...

