Patterning the Body Plan: Drosophila
Lecture Key points
Drosophila has provided a powerful model in which to identify genes that regulate development and then characterize the mechanisms by which their proteins act
The Nobel prize winning work of Nusslein-Volhard, Wieschaus and Lewis illustrated how one can use genetics to identify the proteins involved in a complex process—in this case the development of the embryonic body plan
Transcription factors can act in a regulatory cascade to set cell fate
Transcription factors can have graded effects on gene expression based on levels of expression
The Hox genes and the transcription factors they encode play a conserved role in setting up anterior-posterior fates all along the body axis
Notch signaling provides an example of how contact dependent signaling by a transmembrane ligand can drive binary decisions, and its signal transduction pathway, in which the receptor is cleaved to form a transcription factor, is remarkable
The same genes that regulate embryonic development are often mutationally activated or inactivated in cancer
SAMPLE Learning objectives After this lecture you should be able to:
Contrast Drosophila and the mouse as model systems [largely covered in recitation]
Explain how genetic experiments in Drosophila shaped our understanding of anterior-posterior patterning at the molecular level
Compare and contrast the roles of Bicoid, the gap gene proteins and the homeotic gene proteins
Describe how expression patterns and protein function of the homeotic genes explain selection of segment identity
Illustrate the concept of developmental signaling in binary fate decisions using Notch and Delta as models
Contrast proteins that act “autonomously” and thus mutant cells CANNOT be rescued by neighbors, with those that act “non-autonomously” such that mutant cells CAN be rescued by wild-type neighbors.
Guided Reading Q’s Drosophila has provided a powerful model in which to identify genes that regulate development and then characterize the mechanisms by which their proteins act. The transcription factors regulating early development provide a great example. Read Wolpert Sections 2.1, 2.2 (pp. 37-40) 2.4-2.8 (pp. 41-49) 2.18-2.19 (pp. 66-67), and 2.22 (pp. 72-up to p. 74) answer the following questions about the regulatory cascade of transcription factors that sets cell fates in early Drosophila development.
1) The early Drosophila embryo is a syncytium. This means nuclei are not separated by ______and thus proteins can diffuse across the entire embryo until the point when cells form.
2) How do maternal effect genes differ from zygotic genes? Which type is bicoid?
3) Where within the egg is the bicoid mRNA localized? Contrast that with the localization of Bicoid protein.
4) What is the primary cellular function of Bicoid protein and what is one of its target genes?
5) What is the cellular function of the Gap gene products? The pair-rule gene products?
6) What class of proteins bind to the stripe enhancers of the eve gene?
Many of the genes identified in Drosophila have homologs that play similar developmental roles in us. The Hox genes provided one of the first examples. Read pages Wolpert Sections 2.29-2.32 (pp. 91-94) and answer the following questions on Hox genes in Drosophila.
7) The homeotic selector genes regulate cell fate along the ______body axis.
8) What are the consequences for the embryo’s body plan of deleting the Ultrabithorax gene?
9) What is the cellular function of the homeotic gene products?
Notch signaling is one of the “big five” pathways that influence development of almost every organ and also play important roles in cancer. Read Wolpert Cell Biology Box 5D (p. 212) and Figs. 12.17 and 12.18 (pp. 535, 536) and answer the following questions about Notch signaling.
10) What cell biological characteristic of the Notch ligands Delta, Jagged and Serrate makes signaling in this system “juxtacrine” (i.e limited only to the cells that a signaling cell can directly “touch”)?
11) Signaling in the Notch pathway is amazingly simple—describe how the receptor is directly converted into a transcription factor.
12) Where within the cell would the cytoplasmic domain of Notch be before signaling occurs? How about after signaling occurs?
13) In an embryo that lacks Notch, what would be the result? Too many neural cells OR too many epidermal cells
14) Explore beyond the text—what is a type of cancer in which Notch plays a role?