Growth and Post-Embryonic Development

Tissues can grow by cell proliferation, cell enlargement or accretion.
Often tissues grow by cell proliferation.
Cells such as differentiated muscle or nerve cells growth by increasing their size.
Neurons extend axons and dendrites while muscle cells increase in mass and recruitment of satellite cells.
Accretionary growth, as in cartilage and bone, involves a cell secretion to increase the volume of the extracellular spaces.
Many adult tissues will only divide when induced by injury or other stimuli.
Some tissues such as the  hematopoietic tissues and the epithelia are continually renewed throughout the vertebrate's lifetime.

Cell proliferation: controlled by an intrinsic program & external signals.
The eukaryotic cell duplicates via the cell cycle: M-phase (mitosis), G1 (pre-synthetic interphase), S phase (DNA synthesis), G2 (pre-mitotic interphase).
Growth factors and other signaling proteins are essential for cells to progress through the cell cycle.
Cells must receive such signals not only to divide (see mitotic domains) but for survival & in the absence of growth factors, cell undergo apoptosis.
The cyclins are proteins that control the cell cycle at specific check points.
Cyclins form complexes with and activate cyclin-dependent kinases that then phosphorylates proteins to direct phase-specific events.
Cyclin concentrations oscillate.

Growth of mammals is dependent on growth hormones.
Human embryo increases length from 150 um at implantation to 50 cm at birth.
During first 8 weeks, there is little increase in size but the basic form is laid down.
The greatest rate of growth is at 4 months after implantation.
The head is more than 1/3 of entire length at 9 weeks of gestation, ~1/4 length at birth and ~1/8 length in the adult.
Different parts of the body grow at different rates.
Male and female humans grow at different rates, primarily due to earlier growth spurt in females.

Maternal environment controls fetal growth.
Embryonic growth depend upon growth factors and new born mice lacking insulin-like growth factor 2 (IGF-2) are only 60% of normal birth size.
Growth hormone (GH) is secreted throughout fetal life and secretion by the pituitary begins during the first year of life to control growth.
Growth-hormone releasing hormone (promotes GH synthesis and secretion) and somatostatin (inhibits GH production and release) are both made in the hypothalamus.
GH induces both IGF-1 and IGF-2 which are largely responsible for  both embryonic and post-natal growth.

Growth of long bones occurs in the growth plates.
Developing organs can have their own intrinsic growth programs.
In salamanders, limb size is genetically determined.
The long bones (humerus, femur, radius & ulna) are first laid down as cartilage then become ossified.
Early growth (cell proliferation & matrix secretion) follows a well-defined pattern.
In endochondrial ossification, the cartilage is replaced by bone, starting in the centres (diaphyses) and spreading outward and at secondary centres (epiphyses) at the ends of the bones.

The growth plates are internal regions of the bone, near but not at each end, that are columns of cartilage cells arranged in several distinct layers.
Near the bony epiphysis, is the narrow germinal zone (stem cells), then the proliferative zone, the maturation zone, the hypertrophic zone (size increase) then finally the zone where the cartilage cells die and are replaced by bone laid down by the osteoblasts.
The proliferation of chondrocytes is maintained by Indian hedgehog and parathyroid-hormone-related protein (PHRP).
Growth of the muscles (in length) attached to the long bones depends upon the tension provided by the growth of the long bones.

Cancer can result from mutations in genes controlling cell multiplication and differentiation.
Cancer follows a progression from a benign localized growth to a malignancy where the cells metastasize or migrate to many locations throughout the body and continue to grow.
Genes that can mutate into a form that can contribute to cancer formation are known as proto-oncogenes.
The mutant forms of these genes are called oncogenes.
Tumour suppressor genes are a group of genes that when lost (both copies  inactivated or deleted) will lead to cancer.
Teratocarcinomas arise without alteration to the genetic material and are solid tumours that contain a mixture of many cell types.

Plant growth
Hormones control many features of plant growth and are normally small organic molecules (not proteins).
Auxin regulates a large number of development processes including growth towards light, tissue polarity, vascular tissue differentiation and apical dominance (auxin inhibits growth of lateral buds).
The gibberellins regulate stem elongation.
Cytokinins (adenine derivatives) stimulate growth.
Cell division occurs in the meristem but cell enlargement contributes much to plant growth.

Molting and metamorphosis
Arthropods have to molt in order to grow.
Arthropods cannot grow gradually because they have a rigid cuticle which is secreted by the epidermis.
The process of molting (ecdysis) allows arthropods to increase their size in a step-wise manner.
At the start of a molt, the epidermis separates from the cuticle (apolysis) and molting fluid is secreted into the space.
Cell proliferation & enlargement increases the surface area (folds), new cuticle is secreted then the old cuticle is partly digested, splits then is shed.
Metamorphosis, both insect and amphibian, is under environmental and hormonal control and results in changes in gene expression.

Aging and senescence
Organisms are not immortal.
Over time, senescence, a decrease in physiological functions and an increased susceptibility to stress and disease.
Is senescence the accumulation of a life-time of damage or genetic controlled?
Different life spans of different organisms suggest that is under genetic control.
This is known as the "disposable soma theory" and puts aging into the context of evolution.
Many genes can alter the timing of senescence including  cell cycle genes, DNA replication and repair genes and cell survival genes.
Cells grown in culture, undergo senescence and recent work indicate that telomere integrity may be key.