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Developmental Genetics

Introduction

Developmental Genetics also referred to as Developmental Biology is the study of developmental stages of organisms from the time when the sperm fuses with the ovum through to how an organism develops different organs and finally matures. It studies how genetics influence the process of cell growth, cell differentiation,  and morphogenesis. This branch of biology is almost related to Embryology only that embryology deals with the study of the development of an embryo. It can also be defined as study of plant development from germination to maturity and the genes involved.

Development in Animals.

Formation of an Embryo         

During sexual intercourse, spermatozoa (23 chromosomes), which carry human DNA, are deposited in the vagina of a female. The spermatozoa which are specialized cells with tails to aid movement, travel to the fallopian tube using themotactic and chemotactic gradients to fuse with an ovum - produced as a result of ovulation (23 chromosomes) by the female- in the ampulla (a portion in the upper or middle part of the  of the fallopian tube). This leads to the formation  of a Zygote with 46 chromosomes with a very unique structure of DNA, very different from the DNA of the ovum and the spermatozoon involved in the fertilization. The zygote which is slightly larger than a normal somatic cell immediately start to subdivides through cleavage, a process which is accompanied by a series of mitotic cells divisions, eventually leads to the formation of Blastomeres (a mass of cells) and finally a Blastocyst. At this stage the cell are undifferentiated are basically the same in shape and size. Later the Embryonic Stem cells (ES cells ) are formed which now form the Embryo (6 -7 days after fertilization). It is the embryo that matures to an adult with very differentiated cells that form different organs which perform different function in the body of the animal.

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Transcription factors in the development of an Embryo

Phase 1. Transcription factors in the development of axes

The way an embryo forms its body pattern is determined by how the embryo forms its axes. Three axes formed during axis formation are; Anterior – posterior axis (head- tail), the dorsal-ventral axis (back to belly) and the left – right asymmetry. Development of axes is very important since it determines the development of structures such as limbs, Central nervous system, position of organs like the heart, kidney, liver and the lung. An error in the development of these axis may result in defects such as congenital defects

The development of theses axes in the embryo begins with the first cell divisions which lead to the formation of complex structures with the help of genetically programmed cells. Genes involved in the pattern of organisms include; the Wnt family (e.g. Wnt3 and Wnt5), of the fibroblast growth factor (FGF) family of the transforming growth factor super family (TGF-β) (Tackle, 2003) among others.  These genes are very important for morphogenesis and gastrulation (Tackle, 2003). For instance, bone morphogenic protein-4 (BMP4) is responsible for lateral ventral axis formation in while morphogenetic protein receptor is required for gastrulation in mice embryo genesis (Tackle, 2003). It is also worth noting that the development of the axes follows a specific trend in that left-right axis is established last after dorsal-ventral and anterior-posterior axis have been established. Axis transcription follows some kind of symmetry which is broken at some point leading to the cells on either sides acquiring different behaviours. This breakage in the symmetry is caused by the planar cell polarity which controls cilliary positioning It is also observed that the formation of these axes whether posterior or anterior is governed by the planar cell polarity.

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Phase  2. Segmentation of the Paraxial Mesoderm

In this phase, the Paraxial Mesoderm is divided into two major domains along the anterior-posterior axis. These are the cephalic mesoderm and the cardiac mesoderm (tail and trunk) (Noden, 1991). The cephalic mesoderm is formed in the posterior axis while the cardiac  mesoderm is formed in the anterior mesoderm (Lanza, 2004). The cephalic mesoderm forms the head and caudal mesoderm forms what is known as the ‘tail bud’. The segmental pattern of the segmentation of the paraxial mesoderm is carried out through the production of somites which are transient embryonic segments that give rise to vertebrae, skeletal muscles and the dorsal dermis. Somite formation begins with the bringing of masenchymal cells in the mesoderm. These cells are obtained from the primitive streak and the tail bud. The Wnt genes involved in this process are Wnt-1, Wnt-3a, Wnt-7a, Wnt-8 nad Wnt-11 (Kühl, 2003). This segmentation takes place in three steps. First, is the growth phase in which new paraxial mesoderm cells are produced in the epiblast and blastopore margin and later in the tail bud, all of which are growth zones, and in turn forming two rods of mesenchymal tissue resulting in the formation of the presomitic mesoderm (PSM). This phase is then followed with the phase of patterning which occurs in the PSM. And lastly, is the morphological segmentation phase in which boundaries are formed. This last phase (phase of patterning) is discussed below.

 
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When a caudal presomitic (PSM) mesoderm is formed it usually does not exhibit any segmental pattern. However, it is bestowed with special typed of gens called the cycling genes which exhibit themselves through rhythmic expression in a wave like manner along the the antero-posterior axis of the PSM. As studied in the Xenopus embryos, Thylacine1 which belongs to the family of bHLH genes marks the boundaries and polarity in a segment. This takes place with the help of a PSM enhancer regulated by retinoic acid (RA)  signalling which also activates Thylacine1. RA signalling is a very important contributor of segmentation in this phase as it promotes the anterior segmentation and patterning of the PSM.

Phase 3. Characterization of the Segments

This is best explained using a case study of the Drosophila melanogaster fly

In Drosophila, the Sex combs reduced (Scr) controls the process of segmental characterization of the labial and the prothoracic segments of the embryo as it encodes a “sequence specific transcription factor that control the differentiative pathways in which Scr is expressed” (Gindhart, 1995) . During embryogenesis “Scr accumulation is observed in adiscrete spatiotemporal pattern that includes the labial and prothoracicectoderm, the subesophageal ganglion of the ventral nerve cord and thevisceral mesoderm of the anterior and posterior midgut” (Gindhart, 1995).

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In animals, the process is generally controlled by homeotic genes. The term ‘Homeotic’ was used by an English zoologist to describe the changes that take place in a segment of an animal during development (Brooker Biology). I this phase, the segments formed in the previous phase develop different characteristics the depending of the function they are meant to do (Brooker Biology). A good example of the activity of homeotic gene is the bithorax complex gene in Drosophila. Bithorax complex causes homeotic mutation in the second segment of the developing drosophila insect and determines the number of wings per segment that a given species of  Drosophila is going to have. The homeotic gene are also responsible for the encoding of homeotic proteins with a coding sequence called homeobox. It is important to note that the homeotic gene are also homologous in animal vetertebrates. A good example of these genes in animals are the Hox (HoxA, HoxB, HoxC and Hox D) genes in mice. These proteins are considered important for the development of segment characteristics as they activate transcription of specific genes that promote characterization of the segments (Brooker Biology)

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Phase 4. Cell Differentiation

As used in developmental biology , the term cell differentiation refers to the process by which the less specialised cells become more specialised so that they can perform specific functions. In living things there are a lot of differentiated cells theses include; red blood cells, white blood cells, nerve cells, sperm cells, Female eggs, among others. In this section the paper tries to evaluate the genetic influence on the development of some differentiated cells.

Some animals eliminate chromosomes during embryo genesis through diminution. It is also observed that the separation of chromosomes during anaphase stage is delayed in some animals. In an investigation, it was found that chromosomes were of importance in the process of cell differentiation  during embryogenesis of planariana e.g. Tricaldida. After the alteration of the chromosomes involved there is production of somatic cells whose genetic activities differ from one another. In the same way, there results a difference in the genetic activity of male and female germline. This was discovered by Kahle (1908). This results in a different configuration of chromosomes which are hence called Pseudo-chiasmata. Other animals which are known to exhibit diminution during cell differentiation include; Blow fly (Calliaphora erythrocephala) and copepods. Example of cell differentiated cells include; sperm cell, ovum, cardiac cell, thyroid cell, red blood cell and skeletal muscle cell among others.

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Development in plants

Plant development basically refers to the process of origination of structures and maturity as a plant grows. It must be noted that the process of development in plants has huge fundamental differences compared to those developmental  processes in vertebrate animals.  That is, for vertebrates, when an embryo starts to grow, it has all the body parts that it will eventually have in maturity.  From the very point when the tiniest zygote is hatched, it has all the body parts however small that is, it continues to grow larger and larger and more mature (Tyagi, 2009). On the other hand, throughout their lives, plants continue to produce new tissues and organs from meristems located at the tips of their organs or even between mature tissues.  This includes floral parts that develop even at later stages of such development.

In this study of the biology of plant development the model organism for genetic analysis would be Arabidopsis thaliana.  The Arabidopsis, unlike most plants that have long generation times as well as large genomes, has a generation time of about two months and a genome size of 7 × 107bp. This is particularly similar to Drosophila  and C. elegans. The small genome size of this organism  makes it relatively easy to map the mutant alleles and eventually clone the relevant genes. A flowering Arabidopsis plantis small enough to be grown in the laboratory (Tyagi  2009).

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Remarkably, the morphological  patterns of growth are quite different between plants and animals. For instance, while animal embryos become organised along anteroposterior, dorsoventral, and lateral axes and then subdivide into segments, the form for higher plants are two key features, that is,  the root-shoot axis where the growth occurs at the tips of the shoots and the bottoms  of the roots and secondly the radial pattern in which a plant shoot gives off the buds that gives rise to the branches, leaves and flowers. For example in Arabidopsis growth where initially a rosette of leaves is produced from leaf buds that emanate in a spiral pattern directly from the shoot. The radial pattern is particularly an important mechanism that determines much of the general morphology of the plant.

Moreover, at the cellular level, there is remarkable differences between plant development and animal development. This is picked from the fact that there is no occurrence of cell migration during plant development. In addition the development of a plant does not  rely on morphogens that are deposited asymmetrically in the oocyte. In plants it is possible to regenerate an entirely new individual from most types of somatic cell hence are said to be totipotent, that is, they have the ability to produce an entire individual. On the other hand, animal development invariably relies on the organization within an oocyte as a starting point for development.

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However, despite the differences so clear between plant development and animal development, there are quite a myriad of underlying molecular mechanisms of developments that share a lot of similarities with those of animal growth.  In this study therefore, such similarities are looked into with a view to establishing how genes encoding transcriptions known in plant development play  key roles in plant development.

Plant growth occurs from meristems that are formed during embryonic development. In animal development the earliest stages usually serve to subdivide the embryo into segments that eventually give rise to adult structures. This is simply an expand of the embryo body pattern. In plants the part of adult plants are formed from a group of dividing cells referred to as apical meristems. ( a meristem is simply an organised group of actively dividing cells) the shoot apical meristems grow upwards and give rise to the shoot structures while the root apical meristems grow downwards to produce the roots.

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Plant homeotic genes control flower development. Its noted that although the term homeotic was coined to describe homeotic mutations in animals (Bateson 1926), the first known homeotic genes were described in plants. Many homeotic mutations that affect flower development have been identified in Arabidopsis and also in snapdragon ( Antirrhinum majus). By analysing the effects of many different homeotic mutations in Arabidopsis, Elliot Meyerowitz at the California Institute of Technology and his collegues have proposed the ABC model for flower development, where three classes of genes named A, B, and C govern the formation of sepals, petals, stamens, and carpels. In the outer most whorl (whorl 1), the gene a products are made (Bier 2000). This therefore promotes sepal formation. In whorl 2 both gene A and gene B products are made, which promotes petals formation. In whorl 3, the expression of gene C results in formation of stamen and carpels.

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 Biphenol A.

This is an organic compound with two phenol groups mostly used in the manufacture of polycarbonate plastics and resins. These plastics are mostly used in the making plastic wrappers for food among other numerous uses. Resins on the other hand are used in coating cans pipes.

BPA was firsr synthesised by a scientist called Dodds  in 1930 (Development Bio bk) and is widely known due to its estrogenic effect. In as much as BPA is very useful in some manufacturing industries, it however has some negative effects on animal and in particular human beings.

 One of the effects of BPA is chromosomal abnormality. In their study, Susiarjo, Hassold, Freeman and Hunt (2007) found out that BPA can lead to chromosomal abnormality. They realised that when pregnant mice are exposed to BPA, their ‘grandchildren’ ended up having chromosomal abnormality. This is because “female mammals including- including mice and humans- for m their eggs while still in the mother’s womb. Thus when a ‘grandmother’is exposed to Biosphenol A the children are also exposed”. Exposure of an egg during teh last stages of development causes aneuploidy – a situation in which the daughter cells end up with the wrong number of chromosomes during cell division. This can lead to conditions such as Turners Syndrome and Downs Syndrome in humans.

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When a neonate is injected with BPA, the growth of its epithelial cells height of efferent duct in the testes of just like it affects a young rat. This effect can also be experienced if young human children are injected with BPA.  (Tanabe, Kimoto & Kawato 2006).  It also has significant effect on fetal gonads since it causes a disturbance on the hippocampus as it disturbs the hippocampal neurones during neurogenesis  in the dentate gyrus. (Tanabe, Kimoto & Kawato 2006).

It has been found that BPA also leads to reduced sperm counts in males (Develop Bio Book for Bisphenol A). Its effects can also be traced to major body organs such as the brain, kidney and the testes. This has been investigated by Tanabe, Kimoto & Kawato (2006) in their experiment titled “Rapid Ca2+ signalling induced by Bisphenol A in cultured rat hippocampal neurons”. 

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