CHAPTER 11 The Genetic Control of Development Pattern formation is the key process in development and is the emergence of spatially organized and specialized cells in the embryo from cell division and differentiation of the fertilized egg 11 1 Mating type in yeast illustrates transcriptional control of development The specific mating type of a cell is controlled at the level of transcription S cerevisiae alpha a Mating type alleles MAT alpha and MATa express a set of haploid specific genes Haploid specific genes expressed in cells of both mating types include HO and RME1 When a and alpha are close they prepare each other for mating and undergo fusion LOOK AT NOTES AND MEMORIZE DIAGRAM 11 2 The determination of cell fate in C elegans development is largely autonomous C elegans has two sexes male XO and hermaphroditic XX males fertilize hermaphrodites Development in C elegans exhibits a fixed pattern of cell divisions and cell lineages The hermaphrodite contains 959 somatic cells and the male contains exactly 1031 somatic cells A cell lineage can be illustrated with a lineage diagram Cell fate is determined by autonomous development and or intercellular signaling Cell fate or developmental outcome can be autonomous genetically programmed changes without the need for interactions with other cells or positional information or position of cells within the embryo mediated by signaling interactions between neighboring cells Nematode is largely autonomous transmission of cytoplasmic particles called polar granules P0 to P1 to P2 to P3 The mom 2 gene determines the fate of EMS on P2 The APX 1 gene determines the fate of Abp on P2 through cell surface receptor GLP 1 Developmental mutations often affect cell lineages The division pattern and fate of a cell are affected by more than one gene in more than one type of cell Transmembrane receptors often mediate signaling between cells Alternate alleles of a gene result in opposite cell fates Recessive mutations loss of function mRNA is not produced Dominant mutations gain of function gene is overexpressed Anchor cell AC development of vulva Ventral uterine precursors cell UV If either Z1 or Z4 is burned away ablated the remaining cell differentiates into an anchor cell Lin 12 activity is lacking reduced lin12 0 mutation recessive Z1 and Z4 become anchor cells Lin 12 is overexpressed line12 d mutation dominant Z1 and Z4 become UV cells Lin 12 mutations suggest that the wildtype gene product is a receptor of a developmental signal Lin 12 transmembrane receptor protein separates the lin 12 protein into an extracellular part 13 repeats of EGF epidermal growth factor which contains an amino 3 repeats of cytosine rich domain and an intracellular part which contains a carboxyl 6 repeats of SW16 domain Cells can determine the fate of other cells through ligands that bind with their transmembrane receptors Anchor cell expresses signaling gene called line 3 precursors P4 P8 1 2 and 3 degree lineages Loss of lin 3 absence of vulval development overexpression of lin 3 excess vulval induction Lin 3 ligand binding molecule that binds with an EGF type transmembrane receptor LET 23 LIN 3 transcription factors that determine 1 degree fate Ligand binds with receptors on P5 and p7 adopting 2 degree fate Absence of anchor cell P4 P8 express 3 degree lineage uninduced default state Epistatic interactions between mutant alleles can help define signaling pathways Whereas biochemical pathways are substrate dependent pathways developmental pathways are switch regulation pathways each component stimulates or inhibits activity of the next component in line Stimulate positive regulator and inhibit negative regulator Pathways cannot contain residual activity or genetic redundancy and pathway is linear The type of epistasis observed in the double mutants determines the order of the components in the switch regulation pathway An epistatic gene is a gene whose mutant phenotype masks the mutant phenotype of another gene Like dominance The gene whose mutant phenotype is concealed is a hypostatic gene The product of the epistatic gene acts downstream relative to the product of the hypostatic gene hypostatic gene product acts upstream to that of the epistatic gene Ligands for epidermal growth factor receptors that activate Ras and downstream protein kinases are widespread in the regulation of cell growth and development and have also been implicated in many human cancers Many cancers have mutations analogous to gain of function mutation in let 60 11 3 Development in Drosophilia illustrates progressive regionalization and specification of cell fate Each larval stage is called in instar germ line formed from about 10 pole cells The blastoderm is a flattened hollow ball of cells corresponds to blastula in other animals Cells in the blastoderm have predetermined developmental fates Mutations in a maternal effect gene result in defective oocytes Blockage of transcription of the zygote genome at any time after the ninth cleavage division prevents formation of the blastoderm Mutations that affect oocyte composition or structure can upset development of the embryo Genes that function in the mother that are needed for development of the embryo are called maternal effect genes Development genes that function in the embryo are zygote genes The zygotic genes interpret and respond to the positional information laid out in the egg by the maternal effect genes Mutations in maternal effect genes affect homozygous females eggs cant support normal embryonic development Maternal effect genes establish the polarity of the oocyte before fertilization takes place Embryonic pattern formation is under genetic control Denticles are tiny tooth like projections from the surface of the larva Segments are regions between successive indentations formed by the sites of muscle attachment in the larval cuticle Head C1 C3 Thoracic T1 T3 and Abdominal A1 A8 Parasegments are repeating units consisting of posterior region of one segment and anterior region of the adjacent segment The early stages of pattern formation are determined by genes that are often called segmentation genes because they determine the origin and fate of segments and parasegments Four types of segmentation genes coordinate genes determine axes of embryo gap genes levels of spatial organization mutations absence of segments pair rule genes separation of embryo into segments mutations absence of pattern elements in alternating segments and