Lecture 29 Flashcards
What process determines the final shape autonomic nervous system size of an organism
Growth
Explai the limitations of cell patterning events
Cell patterning events such as the action of morphogens usually occurs over a limited range of no more than 100 cell diameters
What are the three types of growth
Proliferation, cell enlargement and accretion
Explain how growth by proliferation is driven
Growth by proliferation is governed by the cell cycle and the action of cyclins and cdks. There are unique cyclins and cdks to each part of the cell cycle which in turn act on a specific subset of target proteins involved in each stage
Although the mechanisms involved in controlling the cell cycle in mammals is poorly understood, we do know how this occurs in Drosophila. Describe the process of early cell division seen in the developing Drosophila embryo
Initially the cells in the Drosophila embryo are dividing rapidly during the syncytial blastoderm stage. During this stage the G1 and G2 phases are absent from the cell cycles. At cycle 14 however, there is a slowing after the nuclei have migrated to the periphery. These cells then undergo G2 phase and cellularisation. Cellularised cells then adopt their own program of growth depending on which cells they are destined to become.
Explain what is meant by a mitotic domain
A region of cells that will adopt the same growth program
Explain the role of string in governing the cell division in Drosophila embryos
The mitotic domains are controlled by string expression which in turn regulates phosphatases and activated cdks. String is provided maternally in the fertilised egg and drives this early rapid division seen in the syncytial blastoderm stage. Later, string expression is controlled by the patterning genes; gap genes, paired rule genes and segment polarity genes. This accounts for the differential cell divisions seen in each mitotic domain which is subject to the unique combinatorial expression of the patterning genes
Explain how the development of the mesoderm in the Drosophila embryo differs to the model of the other germ layers
In the mesoderm, the tribbles gene prevents the function of string. Tribbles prevents the division of cells in the mesoderm until they have invaginated and gone inside the embryo
Which key signalling pathways are important in regulating cell division
IGF, Hippo and Tor signalling
What is meant when referring to some organs as having intrinsic cues that govern their size
The size of the organ is controlled by cues from within the structure itself. Grafting of tissue from a viable donor source will result in a growth of that structure to the natural size it would have in the donor animal and not the relative size that it should in the recipient
Give some examples of organs that have intrinsic cues that govern their size
Limbs, thymus gland
What is meant when referring to some organs as having extrinsic cues that govern their size
The size of the organ is controlled by cues from elsewhere in the body. Grafted tissue from a donor to a recipient would grow to the size that it would normally in the recipient
Give an example of an organ whose size is governed by extrinsic factors
Spleen
Give an example of how organ growth programs are flexible
In the liver the growth program of the cells can be reactivated. Ablation/removal of up to 2/3 of the liver will result in a complete regeneration of lost structures
Cell number is important in controlling cell growth as the cells need to know how many there are and how many are needed to generate the adult structures, T or F
F - Growth is not driven by a cell counting system and cell number not important in directing growth
Explain the effects of changes in ploidy on cells number and size of an organism
Ploidy affects cell size but not overall size of an animal. Triploid animals will have less cells than their diploid counterparts but will be the same size and shape. The cells themselves will be bigger but there will just be less of them
How do morphogen gradients explain the changes in organism size/shape due to changes in ploidy
The steepness of morphogen gradients is what determine the size of an organ. The steepness of the morphogen gradient remains the same regardless of the number of copies of the gene. Essentially, increasing ploidy just scales up the gradient whilst its steepness is still maintained
The hippo and tor pathways are two key growth control pathways, hippo acts to control cell size whereas tor acts to limit organ size, T or F
F – vice versa
Describe the hippo pathway in the control of growth
Hippo or its vertebrate homologues, Mst1 and 2 acts to limit organ size. When the hippo pathway is inactive the transcription factor Yki (or Yap/Taz in vertebrates) is in the nucleus where it stimulates the growth and survival of cells. When the hippo pathway is activated Yki/Yap/Taz is excluded from the nucleus and growth is prevented
Describe the factors involved in governing the activation of the hippo pathway
Mechanical stress and other signalling pathways (wnts, BMPs etc.) can cause inactivation of the hippo pathway and cause subsequent growth. In contrast, cell-cell contact and polarisation causes an activation of the hippo pathway thereby stopping cell growth
What is the effect of loss of hippo function in invertebrates
Global loss of growth restriction
What is the effect of a double knockout for Mst1/2 in mice
Double mst knockout isn’t as detrimental as it is in invertebrates. It does however cause a massive overgrowth of the liver
Growth rates of different parts of the body do not have to be identical and can differ between different regions and depend on the species, T or F
T
Growth rates in different parts of the body are not uniform, T or F
T
Overall size is governed by two features, what are these
Rate of growth and the duration of the growth
What is seen in the growth rates of humans following birth until puberty
Decrease in the rate of growth
Growth hormone (GH) is the key player in post-embryonic growth. Describe how it is produced and released
GH is produced and released in the pituitary under the influence of growth hormone releasing hormone (GHRH). This is inhibited by somatostatin
Explain the interplay between GH
Growth hormone feeds back on itself to induce expression of somatostatin and block subsequent GHRH expression
Give an example of how the maternal environment governs size in mammals
Crossing shire horses with pony produces different sized offspring depending on which is the mother animal. If the maternal animal is a shire horse a larger fowl will be observed whereas, a maternal pony will give a smaller fowl
Cancer is a loss of growth control, T or F
T
An imbalance between gain and loss of cells can over time have large effect with an excess in cell gain of 5% per year leading to a >4 fold increase in 30 years, T or F
T
What types of tissues are more susceptible to cancer and why
Tissues that are continuously being replaced and have quite an active cell population are most commonly connected to cancer. This is because these cells are already proliferating and each time the genome is copied there is a chance for mistakes to occur that are oncogenic
Often cancers are linked to a failure in the normal proliferation process that occurs during development or maintenance of structures, T or F
F – failure of normal differentiation
Teratomas are a major exception to the idea that a mutation that causes a failure in differentiation causes cancers as they often contains lots of differentiated structures within them, why is this
Teratomas are often caused by mutations that impact the epigenetic regulation of gene expression
Explain the difference between proto-oncogenes and tumour suppressor genes
Both genes can cause cancer if mutated however, whilst proto-oncogenes become oncogenic because of abnormal activation, tumour suppressor genes cause cancer following their inactivation due to mutation.
Give examples of genes that are proto-oncogenes
Raf, Ras, EGFR and Myc
Give examples of genes that are tumour suppressors
Retinoblastoma, p53, Ptc receptor, APC and VHL
Which developmental signals involved in stem cell renewal are also implicated in cancer
Wnt and hedgehog
BRCA2 is another gene associated with cancer but causes it in a different way to proto-oncogenes are tumour suppressors, how does it act
BRCA2 is a gene involved in DNA repair and so mutations in BRCA2 cause faulty repair of other mutations and an increased cancer risk
Explain how dominant cancer syndromes are caused
Patients inherit one inactive copy of a tumour suppressor gene (heterozygotes). Where patients inherit one defective copy of the gene, occasionally in such cells the remaining copy can also become damaged spontaneously. This leads to excessive cell proliferation and can ultimately result in cancer
