Cell and extracellular matrix during the morphogenesis of tissue and organs

I'm not quite sure how this post will go- I think I managed to get the key points, but absolutely none of the details. Apparently this lecture will make more sense after I've watched all of the other lectures of this topic, so stay tuned I guess...?

Describe the sequential events of tissue and organ development during embryogenesis

See previous post: Early Embryology: The First Four Weeks. The most important parts are the formation of the germ layers, and what those layers develop into.

This lecture did give a bit more detail on some tissues, so let's have a look at them here.

Cartilage

Cartilage develops at around five weeks (later than skin, which develops after around four weeks). Mesenchymal cells in the somites condense, forming chondrification centres, which then develop into chondroblasts. Chondroblasts can then differentiate further into hyaline, fibrous and elastic cartilage.

Bone

Bone also develops from the somites of the paraxial mesoderm. There are two main types of ossification (bone formation): intra-membranous ossification and intra-cartilaginous (a.k.a. endochondral) ossification.

Intra-membranous ossification mainly happens in flat bones, such as the bones of the skull. Mesenchymal cells condense within a membrane sheath. Vascularisation then occurs, followed by deposition of the osteoid (bone) matrix.

Intra-cartilaginous ossification mainly happens in long bones. Once again, mesenchymal cells condense, but within cartilage tissue. Cells then hypertrophy (get bigger), and then vascularisation and osteoblast differentiation occur.

Muscles

Muscle development occurs at around seven weeks (with the exception of cardiac muscle, which develops as early as four weeks).

Skeletal muscle is derived from the mesenchymal cells of the myotomes (a type of somite). These cells differentiate into myoblasts, which fuse to become myotubes.

Smooth muscle is mainly derived from the somatopleure (a.k.a. somatic mesoderm) and the visceropleure (a.k.a. splanchnic mesenchyme, assuming that I've interpreted the stuff I Googled correctly- pretty sure the lecturer didn't explain what this was at all). Some mesenchymal cells may also become the myoepithelial cells in glands. Cells destined to become smooth muscle do not fuse, resulting in mononuclear smooth muscle cells.

Cardiac muscle, as I mentioned a few paragraphs ago, develops earlier. It is developed from the lateral plate mesoderm (at least a Google search of "lateral splanchnic mesoderm" returned "lateral plate mesoderm" instead). Once again, no fusion occurs, so each cardiac muscle cell is derived from a single cell.

Transformations

Okay, I'm not referring to a tissue here, but I really didn't know where to put this. Sometimes, cells can become transformed during development. Such transformations include epithelial - mesenchymal transformation (EMT), and occurs in the neural crest, dermis, limb musculature, and some other places. EMT is also of interest as it may be involved in oncogenic (cancer-causing) pathways. There are also mesenchymal - epithelial transformations (MET), such as in the development of kidney tubules, endocardium, and somites.

Describe the role of extracellular matrix and its dynamics in tissue regeneration

I've explored the role of extracellular matrix (particularly ECM stiffness) in previous posts:

• Introduction to Mechanobiology
• Stem Cell Mechanotransduction
• Mechanotransduction in Muscle

I have to admit that this is the part of the lecture where I started zoning out, but I'm pretty sure he was just listing off a bunch of matrix proteins (from structural ones such as collagen, to more specific ones such as growth factors) that could affect tissue regeneration. Also he introduced us to a term called "stem-cell niche," which refers to the microenvironment where stem cells are found (either in vivo or in vitro).

Give examples of the role of growth factors and extracellular matrix molecules in organogenesis.

There are a range of growth factors and other ECM molecules that can affect organogenesis. Growth factors include BMP, TGFβ and Wnt. Other important ECM molecules include those involved in cell adhesion, cell-ECM interactions (e.g. integrin), and cell-cell interactions (e.g. Eph/ephrin family). The main proteins that the lecturer focused on were BMPs (bone morphogenetic proteins) and cadherin, so I guess I'll focus on them here too.

BMPs bind to heparitin sulfate, heparin, and type IV collagen, and aid in a range of processes, such as differentiation, maturation, apoptosis, chemotaxis, mitosis, and ECM production. There are many different types of BMP, and their functions have mostly been determined by using gene knockout techniques. From these techniques, we know that BMP-2 is important in heart formation (embryos can't survive without it), BMP-4 is important in mesoderm formation, and BMP-7 is important in kidney and eye development.

Cadherin, as mentioned here, is integral in cell-cell adhesion. There are several different types of cadherin and, once again, their functions have been determined by using gene knockout techniques. N-cadherin appears to be important in somite and neural tube formation, myocardium organisation, and epithelial - mesenchymal transition. E-cadherin, on the other hand, appears important in mesenchymal - epithelial transition.

*insert random crap about integrin here* No, seriously, I'm not sure what his point was with these slides. Integrin is made up of α and β subunits, and there are lots of different kinds of α and β subunits, which can mix and match to form different types of integrin. Yay?

*Insert more random slides about the history of tissue regeneration and organ transplants* and I think I'm done with this lecture now? Thank goodness for that.