Lecture 7: Developmental Genetics PDF

Lecture 7 Developmental Genetics Developmental genetics is the field that studies the relationships between gene regulation and cell differentiation during development. When an organism undergoes development, a fertilized egg, or some other cel or cells derived from a parent organism si changed in...

Lecture 7 Developmental Genetics Developmental genetics is the field that studies the relationships between gene regulation and cell differentiation during development. When an organism undergoes development, a fertilized egg, or some other cel or cells derived from a parent organism si changed into a new adult organism.  Development involves a process of regulated growth that results from interaction of the genome with the cytoplasm and environment. Development requires a lot of gene actions, considering that every phenotypic trait is an expression of a genotype.  It involves a programmed sequence of phenotypic events typically irreversible. It requires formation of different cell types.  During development, all cells have identical genotypes but regulatory events lead to the production of many different phenotypes or phenoclones. These phenoclones inherit a stable regulatory differentiation state, as well as a genotype, at mitosis. Topics: A. Differential Gene Action: The Basis of Cell Differentiation 1. Pre-transcriptional Control 2. Transcriptional Control Manonggiring, Frenchie 3. Translational Control 4. Post translational Control Robiene, Alyssa Antonette B. Nucleoplasmic Interactions 1. Molecular exchanges between nucleus and cytoplasm Catalo, Kristel 2. Control of macromolecular synthesis in the nucleus by cytoplasm C. Genes and Morphogenesis 1. Gene effects on systems of embryonic induction Nofies, Anthony 2. Gene effects on endocrine systems 3. Gene effects on migrating cells 4. Gene effects on the regulation of growth and metabolism Barloso, Jazmen Presenter: Manonggiring, Frenchie Differential Gene Action: The Basis of Cell Differentiation Pre-transcriptional Control Pre-transcriptional control encompasses the regulatory mechanisms that occur before the initiation of transcription, essentially determining whether a gene will be transcribed or not. This level of control includes various processes such as gene amplification, chromatin condensation, and DNA methylation. Gene Amplification: A process that increases the number of copies of a gene to boost its product. Example: Gall's observations in amphibian oocytes showcased how this mechanism ramps up gene products. Chromatin Condensation The state of chromatin influences gene activity. Euchromatin: Loosely packed, actively transcribing genes. Heterochromatin: Densely packed, transcriptionally silent genes. DNA Methylation Process: Methyl groups are added to DNA molecules. Impact: Typically suppresses gene activity, contributing to long-term gene silencing  Transcriptional control 1. Transcriptional control refers to the regulation of the transcription process itself, influencing how genes are transcribed into RNA. This involves managing the binding of RNA polymerase to DNA, the initiation of transcription, elongation of the RNA strand, and the stability of the resulting RNA transcripts 1. RNA Synthesis Regulation 2. The nucleus manages differential RNA synthesis and degradation. Ensures the right genes are transcribed at the right times, critical for proper cellular function. 3. Developmental Stages in Xenopus laevis Key Observations: Throughout different developmental stages, there’s notable regulation of rRNA synthesis. Conclusions: Highlights how transcriptional control mechanisms adapt during development. Presenter: Robiene, Alyssa Antonette DIFFERENTIAL Gene Action Translational Control and Post Translational Modification  WHAT IS DIFFERENTIAL GENE ACTION? The process by which distinct genes are activated in a cell, providing that cell with a particular purpose that determines its function, is known as differential gene expression. A stem cell develops into a somatic cell with a particular characteristic after differentiating. DIFFERENTIAL GENE ACTION: TRANSLATIONAL CONTROL POST TRANSLATIONAL modification TRANSLATIONAL CONTROL The control of protein synthesis by regulation of the translation step, for example by selective usage of preformed mRNA or instability of the mRNA. Translational regulation can be global or mRNA specific, and most examples of translational regulation that have been described so far affect the rate-limiting initiation step. It could be dependent in the stability of mRNA. The longer the half-life of the mRNA, THE LONGER is the time it can be used during translations.  Over the The rate of past 55 million protein years, the equine synthesis in seafamily has undergone urchins a series of changes was observed that to fluctuate have taken them from having three or four functional toes to developing a single hoof. during the course of development. It was close to zero at and before fertilization, it increased several hundredfold within the first three to four hours after fertilization and declined somewhat before increasing again at the time of gastrulation of the embryo. In addition to the variation of the rate of protein synthesis according to the developmental stage, different amounts of protein are produced at different stages and the kinds of proteins produced change at different stages.  Post-translational modification is a covalent process that changes proteins after they have been POST synthesized. PTMs might involve enzymes or develop spontaneously. TRANSLATIONAL Ribosomes produce proteins by translating mRNA into polypeptide MODIFICATION chains, which can then be modified to generate the complete protein. PTMs have vital roles in cell signalling, such as when prohormones are transformed into hormones.  The regulation of protein structure and function does not stop with the translation of mRNA into polypeptide chain. Epigenetic modification of protein structure generally occurs, since the protein molecule is very large, it may be folded in different ways to generate a variety of three-dimensional conformational states, each with its own characteristic properties.  MODIFICATION MAY PRODUCE SUCH AS: a. Deletion of a part of the peptide chain. b. Changes in the state of oxidation or reduction affecting the structure of the enzymes. c. Attachment of small molecular moiety of the enzymes itself. d. Polymerization and combination with phosphate groups, as in glycogen hosphorylase. Presenter: Catalo, Kristel  WHAT ARE NUCLEOPLASMIC INTERACTIONS? Nucleoplasmic Importance of communication Nucleus & Cytoplasm Interactions between these cellular components Nucleoplasmic interactions refer to Nucleus is the cell's control center, containing Communication between the nucleus and the genetic material (DNA) and regulating cytoplasm is essential for coordinating the communication and exchange processes like gene expression and cell division. cellular activities and ensuring proper of materials between the nucleus It is enclosed by the nuclear envelope, which function. This exchange allows the nucleus (nucleoplasm) and the cytoplasm of controls the movement of molecules in and out to send instructions, in the form of RNA a cell. This process involves the through nuclear pores. and regulatory proteins, to the cytoplasm transport of proteins, RNA, and Cytoplasm is the fluid-like substance for processes like protein synthesis. In other molecules across the nuclear turn, proteins synthesized in the cytoplasm surrounding the nucleus, containing organelles envelope, which separates the such as ribosomes and mitochondria. It is the can enter the nucleus to regulate gene nucleus from the cytoplasm. site of essential cellular functions, including expression and other nuclear functions. protein synthesis, metabolism, and energy production. Together, the nucleus and cytoplasm coordinate to maintain proper cellular function.  KEY PLAYERS Here’s how each contributes Nucleoplasm (nuclear matrix, Cytoplasm (cytoskeleton, Nuclear Envelope chromatin, nuclear bodies) organelles, ribosomes) Nuclear Matrix: Provides structural support Cytoskeleton: Provides a transport network Nuclear Pore Complexes (NPCs): These within the nucleus and organizes chromatin, for molecules once they are released from complexes act as gateways, controlling helping to facilitate processes like DNA the nucleus, guiding them to their the passage of proteins, RNA, and other replication and RNA transcription, which destinations within the cytoplasm. It also molecules in and out of the nucleus. generate the molecules (such as mRNA) assists in positioning the nuclear envelope Large molecules (like mRNA and that need to be transported to the for effective transport. ribosomal subunits) need specialized cytoplasm. Organelles: Once molecules like mRNA or transport mechanisms to pass through Chromatin: The DNA within chromatin ribosomal subunits reach the cytoplasm, these pores. undergoes transcription, producing RNA organelles like ribosomes and the that is then processed and transported out endoplasmic reticulum (ER) facilitate of the nucleus to the cytoplasm for protein protein synthesis, using the instructions synthesis. sent from the nucleus. Nuclear Bodies: Structures like the Ribosomes: After being assembled from nucleolus are involved in the assembly components produced in the nucleus, of ribosomal subunits, which are ribosomes in the cytoplasm translate mRNA into proteins, linking the gene exported to the cytoplasm where expression process between the nucleus ribosomes are assembled and used for and cytoplasm protein production. HOW NUCLEOPLASMIC INTERACTIONS PASSIVE DIFFUSION Small molecules like ions, water, and nucleotides HAPPEN? can move freely between the nucleus and cytoplasm through nuclear pores by passive Nucleoplasmic interactions diffusion. These small molecules don’t require any occur primarily through the special mechanisms to cross the nuclear nuclear envelope, which envelope. surrounds the nucleus. The nuclear envelope contains ACTIVE TRANSPORT specialized structures called Larger molecules, such as proteins, RNA, and ribosomal subunits, nuclear pore complexes require active transport to pass through NPCs. Specific proteins called importins and exportins recognize "tags" or signals on (NPCs), which serve as these molecules (e.g., nuclear localization signals (NLS) or gateways for the transport of nuclear export signals (NES)) and facilitate their passage across molecules between the nucleus the nuclear envelope. Active transport also relies on the Ran GTPase cycle, which provides directionality for the transport and cytoplasm. process.  WHY NUCLEOPLASMIC INTERACTIONS HAPPEN GENE EXPRESSION REGULATION RESPONSE TO SIGNALS The nucleus is responsible for storing and transcribing genetic Cells receive various signals from their environment (such as material (DNA into RNA), but the proteins needed to transcribe DNA hormones or stress signals). These signals often trigger the are often made in the cytoplasm. Conversely, RNA molecules (like movement of proteins from the cytoplasm to the nucleus, where they mRNA) produced in the nucleus must be transported to the regulate gene expression in response to changing conditions. For cytoplasm to be translated into proteins by ribosomes. This back- example, transcription factors may remain in the cytoplasm until a and-forth movement is essential for the continuous flow of genetic signal prompts them to enter the nucleus and activate specific information. genes. COORDINATION OF CELL FUNCTIONS DNA REPAIR AND REPLICATION Cellular processes like growth, division, and differentiation require constant coordination between the nucleus and cytoplasm. For During DNA replication or repair, proteins involved in these instance, during cell division, DNA replication occurs in the nucleus, processes (like DNA polymerase and other enzymes) need to move but the machinery and signals that regulate this process often into the nucleus. The cytoplasm provides many of these proteins, originate in the cytoplasm. Similarly, the ribosomes, produced from which are imported into the nucleus to maintain genome integrity. components generated in the nucleus, are assembled in the cytoplasm.  Genes and Morphogenesis Presenter: Nofies, Anthony  Gene effects on systems of embryonic induction Genes can influence the development of various structures in an organism, focusing on the example of the Sd gene in mice. - The Sd gene affects the development of the tail, rectum, anus, urethra, and genital papilla, as well as the kidneys and vertebrae. - Mice with the Sd Sd genotype lack tails, rectum, anus, urethra, genital papilla, kidneys, and several vertebrae in the lower spinal column. - Mice with the Sd sd genotype have shortened or no tails. - The text highlights the role of the ureter in kidney development, suggesting that it acts as an organizer, guiding the formation of the kidney. - The Sd allele can interfere with the normal elongation and branching of the mesonephric bud, ultimately leading to a reduction or absence of the kidney. This occurs because the organizing tissue fails to induce the necessary tissues to form the capsules and secretory tubules of the kidney.  Gene effects on endocrine system Dwarf mice stopped growing and never reached sexual maturity, while normal mice grew at a normal pace. - Detailed study showed that dwarf mice had a smaller anterior pituitary gland and lacked certain large cells that are normally present in the anterior pituitary gland. - These cells are responsible for secreting the growth hormone. - Experiments where dwarf mice were injected with extracts of normal pituitary glands showed that the dwarf mice grew until they were virtually normal. - This suggests that the pituitary hormone, which regulates growth, is controlled by a single gene.  Cp cp A study of the development of the Creeper fowl revealed the following action the Cp gene and its effects on the phenotype of the fowl: a. It caused a generalized slowing down of growth at about 36 hours of incubation. The structures most affected by the slowdowns were those growing most rapidly at the time: the tissues for the hind limbs. The subsequent development of the embryo was altered, resulting the creeper limbs and smaller body. b. Because of the altered development there is also starvation of the Creeper eye, hence the abnormal Crepeer eye. The study of the Creeper fowl demonstrate that the pleiotropic effects of this mutant found at the completion of development are due to gene-directed changes orginating much earlier in development. It infers that there are changes produced by a genotype which may precede morpaholoagiacal changes. The gene-caused physiological changes may be attributed, in turn, to changes in cellular metabolism, which deals with the biochemical activities associated with cells.