Shaping organisms with apoptosis

Abstract

Programmed cell death is an important process during development that serves to remove superfluous cells and tissues, such as larval organs during metamorphosis, supernumerary cells during nervous system development, muscle patterning and cardiac morphogenesis. Different kinds of cell death have been observed and were originally classified based on distinct morphological features: (1) type I programmed cell death (PCD) or apoptosis is recognized by cell rounding, DNA fragmentation, externalization of phosphatidyl serine, caspase activation and the absence of inflammatory reaction, (2) type II PCD or autophagy is characterized by the presence of large vacuoles and the fact that cells can recover until very late in the process and (3) necrosis is associated with an uncontrolled release of the intracellular content after cell swelling and rupture of the membrane, which commonly induces an inflammatory response. In this review, we will focus exclusively on developmental cell death by apoptosis and its role in tissue remodeling.

Figure 1

Separation of the digits: an example of morphogenetic apoptosis acting as a stone sculptor. A schematic representation of a developing limb is shown with apoptosis indicated in red (up). When cells from the interdigital zones are removed, a new shape is revealed (down)

Figure 2

Apoptosis acting as a pulling force. (a; up) Schematic representation of a dorsal view of a Drosophila embryo during dorsal closure. Apoptotic cells are indicated in red (in the amnioserosa), the force generated by apoptosis in the lateral epidermis is represented by the green arrows. Successive stages of dorsal closure are represented. (a; down) Representation of an apoptotic cells and its closest neighbors at higher magnification. The progressive stretching of the neighboring cells is proposed to be the origin of the pulling force generated by apoptosis on the surrounding tissue.(b) Dorsal closure defects when apoptosis pattern is modified. Dorsal closure can be either accelerated when apoptosis is promoted (left), or slowed down when apoptosis is inhibited (right)

Figure 3

Apoptosis acting as a ‘biological scissor'. (a) Schematic representation of the genital plate of male Drosophila during genitalia rotation. Apoptotic cells (shown in red) allows the initiation of the rotational movement of the inner ring (left, red arrow), then of the outer ring (middle, red arrow). Each ring domain undergoes a 180° rotation. A higher magnification representing the cellular processes taking place at the boundary between the motile ring and the neighboring tissue is shown in the lower panel. Local apoptosis occurs at the boundary and is required to free the motile ring, suggesting its role in tissue detachment. (b) Schematic representation of defects observed when apoptosis is inhibited either in the inner ring (up) or in the outer ring (down) specifically. In each case, the ring in which apoptosis is impaired cannot move, only the other one can rotate leading to a final rotation of 180^o

Figure 4

Morphogenetic apoptosis acting as a ‘metal sculptor'. Schematic representations of the cellular rearrangements taking place during dorsal closure (left) or genitalia rotation (right). Apoptosis is modifying the surrounding tissue, either by creating a force in the tissue or reducing attachment, thus creating a new shape