Genetic Regulation of Development

Genetic Regulation of Development

• Genetic regulation controls embryonic development.
• Factors influencing development include morphogens, growth factors, and signaling molecules.
• Key genes like Hox genes play crucial roles in body plan development.
• Interactions among genes influence the differentiation of tissues and organs.

Embryonic Body Axis Formation

• The dorsal-ventral (D-V) axis formation is determined by the BMP gradient.
• The antero-posterior (A-P) axis formation is regulated by Hox genes.
  • Hox genes exhibit colinearity, where genes expressed at one end are active first, while the expression at the other end follows later.
  • Retinoic acid plays a part in activating anterior Hox genes.
• A morphogen gradient can be generated by a growth factor source, or by an inhibitor source.

Growth Factor Signals

• Growth factor signals direct cells towards new developmental pathways.
• Inductive signals are involved in these pathways.
• BMP4 is a crucial growth factor regulating tissue and cell differentiation.

Homeobox Genes

• Homeobox genes control pattern formation in organisms.
• These genes share a consensus sequence of nucleotides and have a homeodomain.
• Homeobox genes are localized in various ways in the genome; some are scattered, while others are clustered in specific regions.
• These genes are highly conserved, from flies to humans.
• Examples of Hox genes and their functions are mentioned in the notes for anterior-posterior axis formation.

Hox Genes and Body Plan Development

• Hox genes play a significant role in the development of body plans.
• Homeotic transformations can occur due to changes in Hox genes.
• Mutations in Hox genes can lead to the development of different body parts, such as a cervical vertebra transforming into a thoracic vertebra with ribs.
• Hox complexes arose by repeated duplication and mutation of an ancestral homeobox gene.
• They are highly conserved across various species.

Antennapedia Mutations

• Antennapedia mutations can occur in flies, manifesting in the development of antennae being substituted by legs.

Retinoic Acid (RA) Influence on Hox Genes

• Retinoic acid (RA) influences Hox gene expression.
• Overexposure to RA can cause developmental abnormalities in the human fetus, such as missing or defective ears, jaws, and palate, as well as aortic arch abnormalities and deficiencies in the thymus and the central nervous system.
• In mice, overexposure leads to axial truncation and reduced sizes of pharyngeal arches, resulting in deformities.

Cell Communication and Signal Transduction

• Cell-cell communication is controlled by several signal transduction pathways.
• Examples include TGFβ/BMP, Receptor Tyrosine Kinases (FGF, EGF, IGF, Insulin), Wnts, Sonic Hedgehog, Notch, G protein-coupled receptors, and Nuclear hormone receptors.

Neural Tube Divisions

• Pax2/5 and Pax6 transcription factors subdivide the early neural tube into three divisions.

Temporal and Spatial Colinearity

• Vertebrates exhibit temporal and spatial colinearity in Hox genes.
  • Temporal colinearity signifies the sequential activation of genes along the body axis, with earlier-positioned genes being expressed earlier.
  • Spatial colinearity means the genes that are more anterior are expressed prior to those further back along the axis.

Retinoic Acid Receptor

• Retinoic acid receptor is a DNA-binding protein acting as a ligand-activated transcription factor.

Hox Complex and RARE

• Hox complexes contain a retinoic acid receptor response element (RARE) before paralogue 1.
• RARE controls the expression of many genes in the complex.

Pharyngeal Arch 1

• Pharyngeal arch 1 does not have Hox genes.
• It develops into maxillary and mandibular structures

Dental Agenesis

• Hypodontia: missing 1-6 teeth.
• Oligodontia: missing more than 6 teeth.
• Anodontia: complete absence of teeth.
• Genetic defects in genes like MSX1, PAX9, AXIN2, and EDA1 can lead to hypodontia and/or oligodontia.

Msx1 Homeobox Gene

• Msx1 gene plays a role in early expression seen in migrating neural crest cells and the first branchial arch.
• It has a part in initiating odontogenesis.

Pax9 Homeobox Gene

• Pax9 gene plays a critical role in dental formation, especially in early tooth development.
• It is involved in signaling and activating BMP4 expression, which then further controls MSX1.

Axin2 Gene

• Axin2 regulates the stability of β-catenin when cells receive Wnt signals.
• Changes in Wnt signaling can lead to colorectal cancer and cause severe oligodontia.

EDA1 Gene

• EDA1 gene mutations affect ectodermal structures, leading to traits like ectodermal dysplasia (HED) which features features like hypoplasia or absence of sweat glands, sparse hair, dry skin, and oligodontia (multiple missing teeth).

Sonic Hedgehog

• Sonic hedgehog (Shh) is involved in enamel knot formation and later stages of tooth development.
• Gli transcription factors mediate the effects of Shh.

Bone Morphogenetic Proteins (BMPs)

• BMP expression is associated with epithelial-mesenchymal interactions in tooth and organ development.
• BMP4 expression moves from epithelium to condensing dental mesenchyme during odontogenesis, suggesting a potential role in inducing odontogenic potential.

Fibroblast Growth Factors (FGFs)

• FGF4, FGF8, and FGF9 are expressed in epithelial cells during tooth morphogenesis.
• Expression of FGF8 persists until the bud stage, FGF4 is up-regulated at cap stage, and FGF8 and FGF9 are earlier in initiation of tooth development.

Enamel Knot

• Non-dividing epithelial cells forming a transient population appear during the late bud stage at the spots of primary tooth cusps.
• The enamel knot expresses Bmp-2, Bmp-7, Shh genes initially, and BMP4 later during the cap stage.
• There are multiple models of functions based on different factors.

Supernumerary Teeth

• Supernumerary teeth are additional teeth beyond the normal set.
• Caucasians have supernumerary teeth in 0.2-0.8% of cases in their primary, and 1.5-3.5% in permanent dentition.
• Premaxillary conical midline teeth (mesiodens) are the most common.
• There can be an association with clefts of the anterior palate, and dental invaginations.

Cleidocranial Dysplasia (CCD)

• CCD is a genetic disorder associated with missing or partial clavicles, a prognathic mandible, and delayed closure of fontanelles.
• The disorder may also involve supernumerary teeth, delayed eruption of permanent teeth, and bossing of the forehead.

Etiology of Malocclusion

• The etiology of malocclusion is complex and involves both genetic and environmental factors.
• Genetic mechanisms are predominantly involved during embryonic craniofacial development.
• Environmental factors have a larger role in post-natal factors, particularly facial growth

Factors Influencing Human Dental Anomaly

• Dental anomalies are influenced by a multitude of factors, including genetic, epigenetic, and environmental factors acting jointly.

Explore the intricate world of genetic regulation in embryonic development. Learn about the key players such as Hox genes, growth factors, and morphogens that shape the body plan. Understand how axis formation is influenced by gradients and signals during development.