23 an introduction to genetic analysis.docx

1、23 an introduction to genetic analysisChapter 23Developmental GeneticsKey ConceptsA programmed set of instructions in the genome of a higher organism establishes the developmental fates of cells with respect to the major features of the basic body plan.Developmental pathways are formed by the sequen

2、tial implementation of various regulatory steps.The zygote is totipotent, giving rise to every adult cell type; as development proceeds, successive decisions restrict each cell lineage to its particular fate.Gradients of maternally derived regulatory proteins establish polarity along the major body

3、axes of the egg; these proteins control the local transcriptional activation of genes encoding master regulatory proteins in the zygote.Many proteins that act as master regulators of early development are transcription factors; others are components of pathways that mediate signaling between cells.S

4、ome fate decisions are made autonomously by individual cells; many fate decisions require communication and collaboration between cells.The same basic set of genes identified in Drosophila and the regulatory proteins that they encode are conserved in mammals and appear to govern major developmental

5、events in manyperhaps allhigher animals.IntroductionIn all higher organisms, life begins with a single cell, the newly fertilized egg. It reaches maturity with thousands, millions, or even trillions of cells combined into a complex organism with many integrated organ systems. The goal of development

6、al biology is to unravel the fascinating and mysterious processes that achieve the transfiguration of egg into adult. Because we know more about development in these organisms, we will restrict most of our discussion to animal systems.The different cell types of the body are distinguished by the var

7、iety and amounts of the proteins that they expressthe protein profile of each cell (that is, the quantitative and qualitative array of proteins that it contains). The protein profile of a cell in a multicellular organism is the end result of a series of genetic regulatory decisions that determine th

8、e “when, where, and how much” of gene expression. Thus, for a particular gene, we are interested in which tissues and at what developmental times the gene is transcribed and how much of the gene product is synthesized. From a geneticists point of view, all developmental programming that controls an

9、organisms protein profiles is determined by the regulatory information encoded in the DNA. We can look at the genome as a parts list of all the gene products (RNAs and polypeptides) that can be potentially produced and as an instruction manual of when, where, and how much of these products are to be

10、 expressed. Thus, one aspect of developmental genetics is to understand how this instruction manual operates to send cells down different developmental pathways, ultimately producing a large constellation of characteristic cell types.This aspect is not all that we want to understand about developmen

11、tal genetics and production of cellular diversity, however. We also want to understand how these different cell types are deployed in a coherent and constructive distributionin other words, how they become organized into organs and tissues and how those organ systems and tissues are organized into a

12、n integrated, coherently functioning individual organism.Central themes of developmental geneticsThe general body plan is common to all members of a species and, indeed, is common to many very different species. All mammalian species have four limbs, whereas all insects have six. But all mammals and

13、 insects must, in the course of their development, differentiate the anterior from the posterior end and the dorsal from the ventral side. Eyes and legs always appear in the appropriate places. Except for severe disturbances that interfere with development, the basic body plan of a species appears t

14、o be quite immune from environmental modification. The study of the basic development of body plan can then be carried out by studying the internal genetic program of the organism without reference to the environment. We should not forget, however, that the study of the genetic determination of thes

15、e basic developmental processes does not provide us with an explanation of the phenotypic differences between individual members of a species. This chapter focuses on the processes underlying pattern formation, the construction of complex form, and how these processes operate reliably to execute the

16、 developmental program for the basic body plan.Logic of building the body planDuring the elaboration of the body plan, cells commit to specific cell fates; that is, the capacity to differentiate into particular kinds of cells. The cell fate commitments have to make sense in regard to the location of

17、 the cell, because all organs and tissues are made up of many cells and the entire structure of an organ or tissue requires a cooperative division of labor among the participating cells. Thus, somehow, cell position must be identified, and fate assignments must be parceled out among a cooperating gr

18、oup of cellscalled a developmental field.Positional information is generally established through protein signals that emanate from a localized source within a cell (the initial one-cell zygote) or within a developmental field. It is the molecular equivalent to establishing the rules for geographic l

19、ongitudes and latitudes. Just as we need longitudes and latitudes to navigate on the earth, cells need positional information to determine their location within a developmental field and to respond by executing the appropriate developmental program. When that positional information has been captured

20、, generally a few intermediate cell types are created within a field. Through further processes of cell division and decision making, a population of cells with the necessary final diversity of fates will be established.These further processesfate refinementcan be of two types. In some situations, t

21、hrough asymmetric divisions of one of the intermediate types of cells, descendants are created that have received different regulatory instructions and therefore become committed to different fates. This can be thought of as a cell lineage-dependent mechanism for partitioning fates. In other situati

22、ons, such fate decisions are made by committeethat is, the fate of a cell becomes dependent on input from neighboring cells and feedback to them through paracrine signaling mechanisms (see Chapter 22). Such neighborhood-dependent decisions are extremely important, because the chemical dialog between

23、 cells ensures that all fates have been allocated and that the pattern of allocation is coherent. The cell neighborhood-dependent mechanisms also provide for a certain developmental flexibility. Developmental mechanisms need to be flexible so that an organism can compensate for accidents such as the

24、 death of some cell. If some cells are lost through accidental cell death, the normal paracrine intercellular communication is then aborted and the surviving neighbors can become reprogrammed to divide and instruct a subset of their descendants to adopt the fates of the deceased cells. Indeed, the r

25、egeneration of severed limbs, as occurs in some animals, is a manifestation of the power of specification versus hard-wired determination in building pattern.MESSAGECells within a developmental field must be able to identify their geographic locations and make developmental decisions in the context

26、of the decisions being made by their neighbors.The consequence of the preceding scenario for development is that the process of commitment to a particular fate is a gradual one. A cell does not go in one step from being totally uncommitted, or totipotent, to becoming earmarked for a single fate. Eac

27、h major patterning decision is, in actuality, a series of events in which multiple cells that are at the same level of fate commitment are, in step-by-step fashion, assigned different fates. As these events unfold, cell proliferation is generally occurring. Thus, if we examine a cell lineagethat is,

28、 a family tree for a somatic cell and its descendantswe see that parental cells in the tree are less committed than their descendants.MESSAGEAs cells proliferate in the developing organism, decisions are made to specify more and more precisely the fate options of cells of a given lineage.Major decis

29、ions in building the embryoA variety of developmental decisions are undertaken in the early embryo to give cells their proper identities and to build the body plan. Some of them are simple binary decisions:Separation of the germ line (the gamete-forming cells) from the soma (everything else).Establi

30、shment of the sex of the organism. (Ordinarily, all cells of the body make the same choice.)These binary decisions tend to be made at one developmental stage and, as we shall see later, are examples of irreversible fate determination.The other major decisions concern multiple fate options and far mo

31、re intricate decision-making pathways; they lead to the complex pattern elements of the body plan, composed almost entirely of the somatic cells. Most of them are specification decisions taken by local populations of cells:Establishment of the positional information necessary to orient and organize

32、the two major body axes of the embryo: anteriorposterior (from head to tail) and dorsalventral (from back to front).Subdivision of the embryonic anteriorposterior axis into a series of distinct units called segments or metameres and assignment of distinct roles to each segment according to its location in the developing animal.Subdivision of the embryonic dorsalventral axis into the outer, middle, and inner sheets of cells, called the germ layers, and assignment of distinct roles to each of these layers.Production of the various organs, tissues, systems, and appendages of the body