Upload
barry-adams
View
214
Download
0
Embed Size (px)
Citation preview
Gene Regulation in Development
• Key process in development is pattern formation = emergence of spatially organized and specialized cells in the embryo
• Spatial organization of gene products determines cell fate
• Genomic developmental program results in differential gene expression and pattern formation
Genetic Control of Cell Lineages
• Lineage = ancestor-descendant relationships among a group of cells
• Lineage diagrams show the cell relationships within a lineage
• Differentiation in cell lineages is under genetic control
• Development in the nematode follows a fixed program of lineage diversification
Gene Regulation in Development
• Cell fate is progressively restricted in animal development
• Fertilization initiates cleavage divisions in embryo to generate multicellular blastula
• Infolding of blastula forms gastrula
• Cell fate is determined by autonomous development and/or intercellular signaling
Gene Regulation in Development
• Cell fate refers to developmental outcome of cells within a lineage
• Autonomous developmental restriction is controlled by genetically programmed changes
• Positional information refers to developmental restrictions imposed by the location of cells in embryo
• Morphogen = controls development
Lineage Mutations
• Division pattern and cell fate are determined by many genes
• Mutations in any of these genes can affect the pattern of development
• Developmental mutations can be classified by their effect on lineages
• Transformation mutations = cells undergo developmental fate characteristic of other types of cells
Lineage Mutations
• Segregation mutations = sister cells or parent-offspring cells fail to differentiate
• These mutations occur because differentiation factors are not distributed properly among cell lineages during cell division
Lineage Mutations
• Loss of function mutations are recessive mutations in development control genes which result in a failure to produce mRNA or protein
• Gain of function mutations are dominant mutations which result in overexpression or inappropriate
Programmed Cell Death
• Programmed cell death (PCD) occurs in developmental pathways
• PCD or apoptosis is a form of cell suicide that removes specific cells as part of pattern formation
• Mutations in cell death genes may cause tissue malformations or abnormal cell growth patterns
Genes in Pattern Formation
• Pattern formation in Drosophila is a model for gene regulation
• Segmental organization is controlled by segmentation genes which specify the pattern of repeat units
• Parasegments contain the posterior region of one segment and the anterior region of the next
Genes in Pattern Formation
Regional differentiation of Drosophila embryo is regulated by coordinate genes that establish polarity due to concentration gradients:
• Anterior genes affect head and thorax• Posterior genes affect
abdomen• Terminal genes affect
both ends
Genes in Pattern Formation
Segmentation Genes:• Gap genes are expressed in a set of
contiguous segments• Pair-rule genes are expressed in alternating
segments• Segment-polarity genes
are expressed in each segment and affect anterior to posterior polarity
Developmental Progression
Early development in Drosophila is controlled by a hierarchy of regulatory interactions in which each gene is controlled by a combination of other genes:
• Coordinate genes regulate polarity• Gap genes regulate regionalization• Pair-rule genes and segment polarity genes
regulate repeat patterns
Homeotic Genes
• Homeotic genes determine segment specification and differentiation
• Imaginal disks in larvae give rise to adult tissues and organs
• Mutations in homeotic genes result in the transformation of one body segment into another
• Homeotic genes are transcriptional regulators
Homeotic Genes
• Homeotic (HOX) genes contain a consensus sequence = homeobox
• Homeobox is highly conserved in evolution = found in many species
• Homeobox sequences encode DNA binding domains important in transcriptional activation
• HOX genes function in regulatory hierarchy
Plant Development
• Development in higher plants uses some of the same mechanisms as in animals
• In higher plants developmental fate of proliferating cells called meristems into vegetative or floral tissue is determined largely by position