Signaling and gene expression are fundamental to cell biology and developmental biology. Although these topics are highly interrelated, they typically appear in separate units in a course. We use a series of short problem-based learning exercises for two complementary purposes: 1) to promote a better understanding of the mechanisms of signal transduction; and 2) to reinforce students' understanding of cell- and tissue-specific gene expression. Moreover, the exercises promote synthesis of these two topics in the context of real biological problems. The first small-group exercise that we present poses questions about the implications of cell- or tissue-specific expression of signaling molecules, encouraging students to synthesize information when thinking about biological systems. The second exercise asks students to apply the principles of signal transduction to interpret data presented in a case study based on mutations in a MAP kinase pathway that cause Noonan syndrome. Both in-class exercises present opportunities for the students and the instructor to assess the students' understanding of signaling mechanisms. Finally, we include a set of guiding questions on the Wnt signaling pathway as an out-of-class assignment, to be followed by a quiz on Wnt signaling as a summative assessment.