Patterns of senescence and apoptosis during development of branchial arches, epibranchial placodes, and pharyngeal pouches

Background Many developmental processes are coregulated by apoptosis and senescence. However, there is a lack of data on the development of branchial arches, epibranchial placodes, and pharyngeal pouches, which harbor epibranchial signaling centers. Results Using immunohistochemical, histochemical, and 3D reconstruction methods, we show that in mice, senescence and apoptosis together may contribute to the invagination of the branchial clefts and the deepening of the cervical sinus floor, in antagonism to the proliferation acting in the evaginating branchial arches. The concomitant apoptotic elimination of lateral line rudiments occurs in the absence of senescence. In the epibranchial placodes, senescence and apoptosis appear to (1) support invagination or at least indentation by immobilizing the margins of the centrally proliferating pit, (2) coregulate the number and fate of Pax8+ precursors, (3) progressively narrow neuroblast delamination sites, and (4) contribute to placode regression. Putative epibranchial signaling centers in the pharyngeal pouches are likely deactivated by rostral senescence and caudal apoptosis. Conclusions Our results reveal a plethora of novel patterns of apoptosis and senescence, some overlapping, some complementary, whose functional contributions to the development of the branchial region, including the epibranchial placodes and their signaling centers, can now be tested experimentally. Key Findings In embryonic mice, both cellular senescence and apoptosis contribute to the invagination of branchial clefts and the deepening of the cervical sinus floor. Apoptotic elimination of mammalian anamniote lateral line sensory system rudiments occurs independently of cellular senescence. Cellular senescence and apoptosis together support varying degrees of epibranchial placode invagination and detachment of epibranchial placode 3 from the surface ectoderm. Cellular senescence and apoptosis of Pax8‐expressing progenitors help determine the delamination sites of epibranchial neuroblasts and promote epibranchial placode regression. Postulated epibranchial signaling centers in the pharyngeal pouches appear to be inactivated rostrally predominantly by cellular senescence, but caudally predominantly by apoptosis.