In this research, we aimed to investigate the movement of problem significations in the Didactic Approach of Research Teaching from the contributions of the cultural-historical perspective. Methodologically, our work was organized in two stages: the first one comprises the Vygotskian theoretical discussions about the notion of problem based on humanization, focusing on the process of signification in the pedagogical dimension. From this perspective, we identified and discussed some elements that may help potentializing the signification process of second order mediating problems, that is, conceptual problems, whose selection criterion is related to sciences' themes or contents. These elements have been denominated signifying elements, namely: needs, contradictions, collaborations and imaginations. From these discussions, we seek to analyze the notion of problem in teaching by investigation, as well as its role and function in the Sequences of Investigative Teaching. We found two notions of problems in this teaching approach, situated in the perspective of Scientific Literacy, which are: the didactic problems, that are elaborated previously by the teacher to be implemented in the classroom, whose selection criterion is conceptual and the new problems, that arise during the activity's implementation, that is, emerge from the interactions student-student and student-teacher. The second stage of the research consisted in the qualitative analysis of a sciences' research class, integrated to an Investigative Teaching Sequence, called Navigation and Environment, carried out with 3rd year elementary school students of a municipal school of São Paulo, Brazil. Among the empirical results, we highlight that the movement of signification of the didactic problem occurred in three great moments: the first was marked by the transformation of the mediating function of the DP into object of knowledge, becoming the motive of the activity. The second moment was marked by the tensions experienced by the students and the teacher in facing the didactic problem. At this point, different senses of the DP were attributed by the students, just as different PSP emerged from the relation in coping with the didactic problem, mediating and potentializing the DP's signification process. The third and last moment of signification of the DP was marked by its resolution based on the DP's simulation strategy used by the teacher. Based on the theoretical-empirical results, we defend the thesis that the Didactic Problems commonly addressed in proposals guided by the principles of research teaching can present aspects that involve humanization from Vygotsky 's point of view, from the relation established with the signifying elements: needs, contradictions, collaborations and imaginations, manifested in the PSP. The Didactic Problems, therefore, can be qualified as signifying conceptual problems, close to a significant social practice for the students to investigate, since different PSP emerge from the tensions experienced in the classroom, provoked b...