Developmental Biology Lesson 25

Developmental Biology - Lesson 25

• Chapter 20 covers intermediate and lateral plate mesoderm, specifically focusing on heart, blood, and kidneys development.

Mesodermal Lineages

• Mesodermal lineages are determined by BMP4 levels, with lower levels centrally/medially and higher levels laterally.

Intermediate Mesoderm

• This gives rise to the kidney.

Lateral Plate Mesoderm

• This develops into heart, blood vessels, and blood.

Kidney Development

• Pronephros: Initial kidney tubules form.
• Mesonephros: Pronephros undergoes apoptosis, forming a second set of kidney tubules.
• Metanephros: Mesonephros undergoes apoptosis, and final kidney tubules form through reciprocal interactions between metanephrogenic mesenchyme and the ureteric bud.

Reciprocal Induction

• Metanephric mesenchyme induces ureteric bud branching.
• Mesenchyme condenses around ureteric bud tips.
• Mesenchyme aggregates, cavitates, and forms epithelial structures, developing nephrons and collecting ducts.
• These processes involve reciprocal interactions between these tissues.

Kidney Branching

• Tubule branching significantly increases over time (in vitro models).

Molecular Mechanisms of Reciprocal Induction

• Ureteric bud growth relies on GDNF and its receptors.
• GDNF is secreted from metanephric mesenchyme.
• Target cells express Ret (GDNF receptors).

Glial-Derived Neurotrophic Factor (GDNF) Effect

• GDNF signaling from metanephric mesenchyme induces branching of ureteric buds.
• Experimental models using control beads (vs. GDNF-soaked beads) show changes in branching patterns in developing kidneys.

Wnt Signaling in Kidney Development

• Multiple Wnt proteins are involved, especially in ureteric bud-in stalk or tips.
• Without Wnt, kidneys are typically absent.
• Wnts promote mesenchymal condensation around ureteric buds and mesenchyme-to-epithelial transition to form nephrons.

Circulatory System Development

• Formed from lateral plate mesoderm.
• Includes heart, blood vessels, and blood.
• Heart is the first functional organ in the embryo.
• Heart progenitor cells migrate to form cardiogenic fields, leading to development of a functional heart.

Inductive Interactions and Cardiogenic Mesoderm

• Wnt signaling guides lateral plate mesoderm to form blood and blood vessels.
• Wnt inhibitors (Dkk, Crescent, and Cerberus) block Wnt signaling, allowing BMP and FGF8 to develop cardiogenic mesoderm.
• BMP is vital for heart and blood cell differentiation.
• Noggin and Chordin from the notochord prevent heart and blood field formation in the embryo's center.

Heart Primordia Migration

• Cardiac progenitors migrate between ectoderm and endoderm.
• Fibronectin guides cardiac precursors during migration.
• Initially, two separate heart fields exist and then fuse.

Retinoic Acid and Hox Genes

• Posterior portions of heart fields express retinoid acid.
• Retinoic acid gradient regulates Hox gene expression.
• Specific Hox genes promote regional identities within heart fields.

Cardiac Looping and Chamber Formation

• Looping positions the atria anterior to the ventricles, setting up right-left orientation.
• Specific gene expression happens before and after looping, leading to chamber differentiation.
• Endocardial cushions form at atrioventricular canal and outflow tract.
• Genetic factors, like Twist, and cells, like neural crest cells, guide development.

Vasculogenesis and Angiogenesis

• Vasculogenesis forms blood islands (primary capillary networks) with hemangioblasts.
• Angiogenesis expands the vasculature network via remodeling of blood vessels, creating new blood vessels.
• Paracrine signals and receptors guide these processes.

Extraembryonic Vasculogenesis

• Occurs in the yolk sac.
• Forms early vasculature and red blood cells.
• May generate definitive adult blood stem cells (mouse studies)

Intraembryonic Vasculogenesis

• Creates the dorsal aorta, connecting with capillary networks in organs.
• Dorsal aorta scaffold is derived from somite cells.

VEGF Signaling in Angiogenesis

• VEGF (vascular endothelial growth factor) drives capillary network remodeling.
• VEGF induces endothelial migration, expansion of capillary networks, and tip cell response (sprouting of new vessels).
• VEGF balance is crucial for proper vascular development to prevent diseases such as pre-eclampsia.

Hematopoiesis and Stem Cell Formation

• Hematopoiesis is blood cell generation from stem cells.
• Stem cells divide to create stem cells and progenitor cells that become different blood cell types.
• Hematopoietic stem cells are pluripotent, producing all blood cell types.
• HSCs originate in the aorta-gonad-mesonephros region (AGM) and migrate to the bone marrow.

HSC Niche

• HSC survival and function are dependent on the bone marrow niche, which includes perivascular/endothelial cells that produce SCF (stem cell factor).

Hematopoietic Lineage Hierarchy

• Stem cells divide to become multipotent progenitors, then oligopotent progenitors, and eventually lineage-committed progenitors, ending in mature blood cells such as erythrocytes, platelets, eosinophils, monocytes, dendritic cells, NK cells, B cells, and T lymphocytes.

Explore the intricate processes involved in the development of intermediate and lateral plate mesoderm as covered in Chapter 20 of Developmental Biology. This lesson specifically focuses on the formation of the heart, blood vessels, and kidneys, detailing key concepts like mesodermal lineages and reciprocal induction in kidney development.