BIOL 4330 1st Edition Lecture 13 Outline of Last Lecture I. InductionII. The 3D Coordinate System of the LimbIII. Roles of AERIV. Limb FormationOutline of Current Lecture I. System Theory BiologyII. Gene Regulatory NetworksIII. Six General Principles of Systems Biology IV. MetamorphosisV. Regional Specific Development PatternsCurrent LectureThe systems theory approach attempts to understand the principles behind biological organization and to relate the different levels of biological hierarchy (atom, molecule, gene, cell, tissue, organ, organism, ecosystem) to one another.Systems biology is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are rigorous as our reductionist programs, but different. It means changing our philosophy, in the full sense of the term.Developmental biology studies the initiation and construction of organisms rather than their maintenance. Developmental biology is an integrative field: it goes from the molecular/ chemical levels, through the cellular and organ systems to the ecological and evolutionary levels.Gene Regulatory Networks1) Identity of the cell lineage2) When and where specific genes are expressed3) The mechanisms regulating expression4) Gene expression measurements when genes are blocked or overexpressedThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Simple GRN Signals (TFs= transcription factors) in different locations in the embryo, activate different regulatory genes and the protein encoded which will activate different batteries of structural genes.Six General Principles of Systems Biology Applied to Developmental Biology 1) Context-dependent properties In embryology the parts being determined by the whole - e.g. the fate of a cell is specified by its position. E.g. BMP4 (roles in bone formation, apoptosis, epidermis formation)..words take on meaning in context. 2) Level Specific Properties & Emergence The properties of a system at any given level of organization cannot be explained by those levels “below” it – e.g. temperature is not a property of an atom, but emerges from an aggregate of atoms.3) Heterogeneous Causation Causation is seen as being both “upward” from the genes to the environment, & “downward” from the environment to the genes. What a cell is depends both onits genes & on the cells surrounding it. E.g. whether a turtle becomes female or male depends on temperature. 4) Integration Understanding biology requires synthesis as well as analysis (organicism and reductionism). E.g. neither mother nor the fetus are seen as an entity separate from each other.5) Modules and Robustness - The organism develops as a system of modules. Robustness (canalization) refers to the ability of an organism to develop the same phenotype despite perturbations from the environment or from mutations – a function of the interactions within & between the modules. ---- The embryo is a “complex adaptive system”. E.g. modular enhancer sequences at the genetic level – but there is redundancy – e.g. the eye could form in more than one way; - also segment polarity genes in Drosophila –changing one still leads to proper segmentation 90% of the time.6) Homeorhesis The task of developmental biologists is to understand homeorhesis- how the organism stabilizes its different cell lineages while it is still constructing itself. ---vs. a physiologist who attempts to understand the interactions among parts that exist throughout the life of the organism – or homeostasis, how the organism maintains itself. ----Development is like a ball rolling down a hill, a cell eventually finds itself in a basin – a stable state (attractor state) where arobust and stable configuration of gene expression becomes possible (Waddington 1957) E.g. theability of a set of transcription factors (TFs) to rearrange transcriptional networks to convert exocrine pancreas and liver cells into endocrine pancreas cells (an attractor state)Metamorphosis: the hormonal reactivation of development • Transition of the larval to the adult stage • A large proportion of the animal’s structure changes and the larva and adult are unrecognizable as the same individual• Larval structure and function are specific to their life style/habitat and that often differs from that of the adultHemoglobin: T3 replaces the population of larval blood cell progenitor cells with a population of adult blood cell progenitor.Thyroxine (T4) serves as a prohormone – secreted into the blood by the thyroid gland. It is converted in the peripheral tissues to the active hormone T3 by the enzyme deiodinase II in the target tissues where they Bind to Thyroid hormone receptors TRα & TRβ T3 can be inactivated by deiodinase III which converts T3 into di-iodothyroxine and then to tyrosine.Regional Specific Developmental Patterns • By regulating the amount of T3 and TRs (thyroid hormone receptors) in their cells, the differentregions of the body can respond to thyroid hormones at different times. • The type of response (proliferation, apoptosis, migration) is determined factors present in the tissues. • The same stimulus causes some tissues to degenerate while causing others to develop and differentiate (e.g. tail degeneration)Heterochrony is defined as the phenomenon wherein animals change the relative time of appearance and rate of development.Neotony- refers to the retention of the juvenile form as as result of retarded bidy development relative to the development of the germ cells and gonads (which achieve maturity at the normal time).Progensis- also involves the juvenile for, but the germ cells and gonads develop at a faster rate than normal, becoming sexually mature while the rest of the body is still a juvenile.Direct Development- the embryo abandons the stages of larval development entirely and proceeds to construct a small adult.Four Types of Regeneration -Stem cell mediated regeneration- stem cells allow an organism to regrow certain organs or tissues that have been lost – e.g. planarians. Hair replacement and blood cells. -Epimorphosis - e.g. regerating limbs, tissues differentiate into a regeneration blastema, divide, and redifferentiate into the new structure-planarian flat worm -Morphallaxis (e.g. hydra)-there is a repatterning of existing tissues with little or